IL-6 In Lung Tissue Research Articles

Particulate matter with a diameter of ≤2.5 μm induces and enhances bleomycin-induced pulmonary fibrosis by stimulating endoplasmic reticulum stress in rat.

This study was designed to investigate the effect of particulate matter with a diameter of ≤2.5 μm (PM2.5) on bleomycin (BLM) induced pulmonary fibrosis. Thirty-two Sprague Dawley rats were assigned into four groups (intratracheal instillation of 500 μL of PBS (control), 2 mg/kg PM2.5, 3.5 mg/kg BLM A5, and BLM plus 2.0 mg/kg PM2.5) and were fed for 14 days. All rats were sacrificed after the study. Lung tissues and bronchoalveolar lavage fluid were prepared for histological and biological analysis. We found that PM2.5 caused dose-trend pulmonary alveolitis and fibrosis. Histological scores, expression of α-SMA and Collagen I as well as contents of TNF-α and IL-6 in lung tissues were upregulated by treatment of PM2.5. PM2.5 did not change the percentage of neutrophils and macrophages. The expression of endoplasmic reticulum (ER) stress markers Chop and GRP78 was upregulated by treatment of PM2.5. In comparison with either PM2.5 or BLM treatment, BLM plus PM2.5 treatment induced higher histological scores, higher expression of α-SMA, collagen I, TNF-α, IL-6, Chop, and GRP78, with increased neutrophil counts and decreased macrophage counts. We concluded that PM2.5 instillation caused pulmonary alveolitis and fibrosis by stimulating ER stress responses in rat. PM2.5 also showed a synergistic effect on BLM-induced pulmonary fibrosis.

Glycyrrhizin administration ameliorates Streptococcus aureus-induced acute lung injury

Streptococcus aureus (S. aureus)-induced acute lung injury (ALI) has a high incidence of mortality clinically. Glycyrrhizin (GL) is a traditional Chinese medicine for anti-inflammatory. However, the role of GL in S. aureus-induced ALI has not previously been elucidated.GL (25 mg/kg i.p.) administration exerts potent anti-inflammatory effect in this model. GL administration significantly alleviated inflammation via reduction of multiple cytokines (serum and lung tissue IL-6, TNF-α, IL-8, IL-1β and HMGB1) and immune cells (lung tissue neutrophil and macrophage infiltration). Additionally, we measured the signaling pathways (NF-kB and MARKs) and inflammasome dependent pyroptosis. The results suggest that GL inhibits NF-kB, p38/ERK pathways and pyroptosis. Furthermore, we used different inhibitors to treat infected-A549 cells and found that BMS-582949 (a p38 inhibitor) is the most effective inhibitor for inhibiting pro-inflammatory cytokines (IL-6, TNF-α and IL-1β) production, which suggests that p38 signaling pathway might be the main pathway for S. aureus-induced inflammation.Collectively, the data demonstrates that GL could mitigate inflammation after S. aureus infection.

The interventional effects of saturated hydrogen saline on lung injury in rats with cecal ligation and puncture operation

To investigate the hypothesis that hydrogen could ameliorate cecal ligation and puncture (CLP)-induced lung injury of rats by inhibiting cystathionine-gamma-lyase/hydrogen sulfide (CSE/H2S) system. A total number of 24 healthy male SD rats weighting 250～300 g were randomly divided into four groups (n=6 in each group): sham operation group(sham group), hydrogen-rich saline control group(H2 group), CLP group and hydrogen-rich saline treatment group(CLP+H2 group). The rats were treated with hydrogen-rich saline or saline 10 min before CLP or sham operation. At 8 h of sham or CLP operation, lung samples were obtained to detect the changes of the CSE/H2S system using biochemical and RT-PCR methods. In order to further confirm the role of H2S during hydrogen improve the lung injury of CLP rats, we also observed the effect of hydrogen-rich saline on the lung injury induced by H2S donor-sodium sodium hydrosulfide (NaHS). Thirty-two healthy male SD rats (250~300 g) were randomly divided into four groups (n=8 in each group): control group, H2S group, H2S+H2 group and H2 group. Saline(10 mg/kg) or NaHS(H2S donor, 56 μmol/kg) was injected intraperitoneally (10 mg/kg) respectively into rats in the control rats or H2S group. For rats in the H2S+H2 and H2 group, hydrogen-rich saline (10 mg/kg) was injected 10 min before saline or NaHS administration. Eight hours after the LPS saline or NaHS administration, lung coefficient, MDA content, and MPO activity were detected. The contents of TNF-α, IL-6 and IL-10 in lung tissue were measured, and the morphological changes of lung tissue were also observed. CSE/H2S system up-regulating were observed in animals exposed to CLP. Hydrogen-rich saline treatment significantly inhibited CSE/H2S system as indicated by significantly reduced H2S production in lung, along with a decreased CSE activity and CSE mRNA expression (all P＜0.05). Importantly, the results showed that lung injury and lung tissue inflammation were observed in animals exposed to NaHS. Hydrogen-rich saline treatment significantly attenuated lung injury as indicated by significantly improved histological changes in lung, significantly reduced index of quantitative assessment (IQA), MDA content and lung coefficient (all P＜0.05). MPO activity in lung tissue was significantly reduced along with decreased productions of TNF-α and IL-6, and an increased production of IL-10 in the presence of hydrogen (all P＜0.05), demonstrating antioxidant and anti-inflammatory effect of hydrogen in NaHS-induced ALI. These results indicate that hydrogen-rich saline peritoneal injection improves the lung injury induced by CLP operation. The therapeutic effects of hydrogen-rich saline may be related to suppressing the production of H2S.

Pirfenidone inhibits epithelial-mesenchymal transition and pulmonary fibrosis in the rat silicosis model

To study the role of pirfenidone in rats exposed to silica dust, we established the rat silicosis model with 50 mg/ml silica by intratracheal instillation. From the first day after silica instillation, rats were given pirfenidone (50, 100 mg/kg/day) and rats were sacrificed at 14 days and 28 days to observe the histopathology of lungs, to analyze the level of TNF-α, IL-1β, IL-6 in lung tissues and to measure the expression of TGF-β1, Smad2/3, vimentin, and E-cadherin in lung tissues. Results showed that pirfenidone (50, 100 mg/kg/day) reduced the silica-induced alveolar inflammation, the damage of alveolar structure and the blue areas of collagen fibers in the lungs of rats. At the same time, pirfenidone also reduced the level of TNF-α, IL-1β, IL-6 in lung tissues and the protein expression of collagen I. After pirfenidone intervention for 14 days and 28 days, the protein expression of vimentin was down-regulated and the protein expression of E-cadherin was up-regulated in lung tissues. In addition, the TGF-β1/smad2/3 pathway was activated at 14 days and 28 days after silica instillation, and pirfenidone reduced the expression of TGF-β1 and smad2/3 in the lungs. These results indicated that pirfenidone intervention inhibited the epithelial-mesenchymal transition and pulmonary fibrosis in rat silicosis model, which effects may be related to the TGF-β1/smad pathway.

MicroRNA-92a antagonism attenuates lipopolysaccharide (LPS)-induced pulmonary inflammation and injury in mice through suppressing the PTEN/AKT/NF-κB signaling pathway

Overwhelming lung inflammation is a key feature of acute lung injury (ALI). MicroRNAs (miRNAs) have been implicated in the regulation diverse cellular processes including the inflammatory response. However, little is known about their functions and molecular involvement in regulating the inflammatory process in ALI. Herein, we established a lipopolysaccharide (LPS)-induced ALI mouse model and used miRNA microarray analysis to investigate and compare the miRNA expression profiles in mouse lung tissues. We found that miR-92a was markedly upregulated in the lung tissues of ALI mice compared with that in normal lung tissues. This upregulation of miR-92a in LPS-induced ALI mice was further confirmed in lung tissues, splenocytes and bronchoalveolar lavage fluid (BALF) by quantitative real-time PCR. Inhibition of miR-92a by injection with antagomir-92a markedly reduced LPS-induced pathological changes associated with lung inflammation, and reduces lung wet/dry ratio (W/D ratio), and Evans blue dye extravasation (an indicator of lung epithelial permeability). Moreover, inhibition of miR-92a ameliorated the inflammatory response by reducing the repression of proinflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6 in lung tissues. In addition, we identified that miR-92a inhibited the phosphatase and tensin homolog on chromosome ten (PTEN) by binding to its 3ʹ-UTR in RAW264.7 murine macrophage cells. Western blot analysis demonstrated that inhibition of miR-92a may ameliorate inflammatory response through blocking PTEN/AKT/NF-κB signaling pathway in ALI mice. Collectively, these results have revealed a significant role of miR-92a in the lung inflammatory response associated with ALI in mice, and suggest that miR-92a may have potential as a prognostic indicator and novel therapeutic target for the treatment of ALI in future.

Influences of hypoxia inducible factor-1α on the expression of inflammatory cytokines in mice with influenza A (H1N1) virus infection

Objective To analyze the changes in the expression of hypoxia inducible factor-1α (HIF-1α) and inflammatory cytokines and to investigate the role of HIF-1α in regulating the production of inflammatory cytokines during influenza A (H1N1) virus infection. Methods BALB/c mice were injected with H1N1 virus to establish the mouse model of H1N1 virus infection. Fifteen BALB/c mice were randomly divided into three groups: control group, H1N1 virus group and H1N1 virus+ HIF-1α inhibitor group. Inflammatory cytokines (IL-6, TNF-α, IL-1β and IL-10) in samples of serum and lung tissues were detected by Luminex and ELISA. Levels of HIF-1α in serum and lung tissue samples were detected by Western blot and ELISA, respectively. Results Compared with the control group, the levels of inflammatory cytokines in serum (IL-6, TNF-α, IL-1β and IL-10) and lung tissues (IL-6 and TNF-α) and the expression of HIF-1α in serum and lung tissues in the H1N1 virus group were significantly increased. The levels of HIF-1α, IL-6, TNF-α IL-1β and IL-10 in lung tissues in H1N1 virus+ HIF-1α inhibitor group were significantly lower than those of the H1N1 virus group. Conclusion During H1N1 virus infection, the levels of inflammatory cytokines and HIF-1α were significantly increased. The production of inflammatory cytokines was significantly reduced after inhibiting HIF-1α expression, suggesting that HIF-1α might promote the production of inflammatory cytokines. Key words: H1N1 virus; HIF-1α; Inflammatory cytokines

Mechanism of lung injury of rats induced by inhalation of white smoke from burning smoke pot

Objective: To explore mechanism of lung injury of rats induced by inhalation of white smoke from burning smoke pot. Methods: Forty-eight Sprague Dawley rats were divided into control group (n=12) and injury group (n=36) according to the random number table. Rats in injury group were placed in smoke-induced injury experimental equipment fulled with white smoke from burning smoke pot for 5 minutes to make lung injury, and rats in control group were placed in smoke-induced injury experimental equipment fulled with air for 5 minutes to make sham injury. Six rats in injury group at post injury hour (PIH) 6, 24, and 72 and six rats in control group at PIH 72 were collected to observe pathological changes of lung tissue and pathological score of rats in the two groups by hematoxylin-eosin staining, to detect expression of nuclear factor-κB (NF-κB) p65 mRNA in lung tissue of rats by reverse transcriptional polymerase chain reaction, and to detect content of tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and IL-6 in lung tissue of rats by enzyme-linked immunosorbent assay. Data were processed with one-way analysis of variance and t test. Results: At PIH 72, lung tissue structure of rats in control group was clear and complete, with no inflammatory cell infiltration. At PIH 6, there was edema, hemorrhage, and inflammatory cell infiltration in lung tissue of rats in injury group. At PIH 24, edema, hemorrhage, and inflammatory cell infiltration in lung tissue of rats in injury group aggravated. At PIH 72, area of edema in lung tissue of rats in injury group was enlarged, with obvious hemorrhage and inflammatory cell infiltration. At PIH 6, 24, and 72, pathological score of lung tissue of rats in injury group was (3.43±0.86), (5.39±0.93), and (9.99±0.84) points, respectively, obviously higher than that of rats in control group at PIH 72 [(2.11±0.20) points, t=3.659, 8.450, 22.355, P<0.05]. As time post injury prolonged, pathological scores of lung tissue of rats in injury group were significantly increased (F=121.244, P<0.01). At PIH 6, 24, and 72, expression of NF-κB p65 mRNA in lung tissue of rats in injury group was 15.5±4.3, 25.9±1.8, 30.9±3.5 respectively, significantly higher than that of rats in control group at PIH 72 (7.8±0.8, t=4.315, 20.445, 14.408, P<0.01). As time post injury prolonged, expression of NF-κB p65 mRNA in lung tissue of rats in injury group gradually increased (F=32.691, P<0.01). At PIH 6, 24, and 72, content of TNF-α, IL-1β, and IL-6 in lung tissue of rats in injury group was significantly higher than that of rats in control group at PIH 72, respectively (t=7.650, 8.968, 6.827, 6.726, 8.978, 3.460, 5.420, 13.289, 16.438, P<0.01). At PIH 24, content of TNF-α and IL-1β in lung tissue of rats in injury group was higher than that of rats in the same group at PIH 6 and 72, respectively (t=3.409, -2.549, 4.047, -4.100, P<0.05). At PIH 24 and 72, content of IL-6 in lung tissue of rats in injury group was respectively higher than that of rats in the same group at PIH 6 (t=8.273, 9.711, P<0.05). Conclusions: After inhaling white smoke from burning smoke pot, rats are inflicted with lung injury by increasing expression of NF-κB p65 mRNA and content of TNF-α, IL-1β, and IL-6, and induce pathological changes of edema, hemorrhage, and inflammatory cell infiltration of lung tissue.

The anti-inflammatory effect of hesperetin on lung damage induced by paraquat in rats

Objective: To investigate the anti-inflammatory effect of hesperetin (HSP) on lung damage induced by paraquat (PQ) in rats by detecting the levels of inflammatory makers in rat lung tissues. Methods: 140 Wistar male rats were randomly divided into negative control group, HSP control group, HSP control group, paraquat model group, pirfenidone (PDF) positive control group, and 100, 200, 400 mg/kg HSP treatment groups. All groups were exposed to 50mg/kg paraquat by oral gavage except for the negative control group and HSP control group. After 24 hours, the rats in each group were given drug intervention once daily. 10 rats were randomly sacrificed at 7th day and 28th day after exposure to paraquat respectively. 3 rats were randomly selected from them and HE, Masson staining were used to observe the pathological changes in the lungs of each group. Each group randomly selected 6 rats at two time points to detect the levels of TGF-β(1), TNF-α, IL-4, IL-10, IL-1β and IFN-γ in rat lung tissues. Results: Histopathological examination found that the lung injury were reduced in the rats of PDF positive control group and all HSP treatment groups. Compared with the negative control group, the levels of TGF-β1, IL-1β, TNF-α, IL-4, and IL-10 in rat lung tissues were significantly increased (P<0.05, P<0.01) after PQ exposure at two points in time, and there was no significant difference in the level of IFN-γ in lung tissues compared with the negative control group (P>0.05) . The levels of TGF-β1, IL-1β, IL-4, IL-10 and TNF-α in the lung tissues of rats on the 7th day in different dose treatment groups of HSP were reduced compared with those in the PQ model group with varying degrees (P<0.05, P<0.01) . The level of IFN-γ in lung tissues of rats were not significantly different from that of model group (P>0.05) . The levels of TGF-β(1) and TNF-α in lung tissue of rats on the 28th day in PDF positive control group and different dose treatment groups of HSP were reduced compared with those in the PQ model group with varying degrees (P<0.05, P<0.01). The levels of IFN-γ in the rat lung tissues were increased compared with those in the PQ model group (P<0.05). Besides, there were no significant in the levels of IL-1β, IL-4 and IL-10 in lung tissues compared with PQ model group (P>0.05). Conclusion: HSP can reduce lung damage induced by PQ in rats by inhibiting the release of inflammatory factors and promoting the secretion of anti-inflammatory factors.

Effect of therapeutic hypercapnia preconditioning on lung ischemia-reperfusion injury in rats

Objective To evaluate the effect of therapeutic hypercapnia preconditioning on lung ischemia-reperfusion (I/R) injury in rats. Methods Forty healthy adult Sprague-Dawley rats of either sex, aged 2 months, weighing 250-300 g, were divided into 5 groups (n=8 each) using a random number table: sham operation group (group S), group I/R and preconditioning with therapeutic hypercapnia of different level groups (group THP1-3). Lung I/R injury was induced by clamping the left hilum of lung for 45 min followed by 120 min of reperfusion.In THP1-3 groups, the respiratory parameters were adjusted at 5 min of stability after isolating the left hilum of lung to make PETCO2 reach 55-65, 65-75 and 75-85 mmHg respetively and maintained at this level for 5 min, normal ventilation was then used to make PETCO2 restore the normal level, continuously repeating for 3 circles, and then the left hilum of lung was blocked for 45 min followed by 120 min of reperfusion.The bronchoalveolar lavage fluid (BALF) was collected at the end of reperfusion for determination of the total protein (TP) concentration using Coomassie brilliant blue staining.Lung tissues were obtained at the end of reperfusion for examination of pathological changes after haematoxylin and eosin staining (under a light microscope) and for determination of wet/dry weight ratio (W/D ratio), malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, interleukin-8 (IL-8) and IL-10 contents (by enzyme-linked immunosorbent assay), tumor necrosis factor-alpha (TNF-α) expression (by immunohistochemistry) and expression of TNF-α mRNA (by real-time polymerase chain reaction). Results Compared with group S, the TP concentration in BALF, W/D ratio and contents of MDA, IL-8 and IL-10 in lung tissues were significantly increased, the SOD activity was decreased, the expression of TNF-α mRNA was up-regulated (P 0.05), the staining range and intensity of TNF-α were decreased, and the pathological changes of lung tissues were significantly attenuated in THP1-3 groups. Conclusion Therapeutic hypercapnia preconditioning can reduce lung I/R injury in rats, and the mechanism is related to inhibiting inflammatory responses and oxidative stress responses. Key words: Hypercapnia; Reperfusion injury; Lung; Preconditioning

Effect of a 12-week submaximal swimming training in rats exposed to tobacco- derived nitrosamine ketone.

Background:Tobacco contains carcinogens such as NNK (nicotine-derived nitrosamine ketone) that makes induction of lung cancer by changing the stimulation of IL-10 expression. The aim of this study was to investigate changes in resting levels of IL-10 in lung tissues of rats exposed to NNK after a 12-week aerobic submaximal swimming training.Methods:For this purpose, 46 Wistar rats were randomly divided into five groups consisting training, training + NNK, NNK, saline and control. NNK-induced groups received NNK subcutaneously one day per week at a rate of 12/5 mg per kg body weight and the training groups performed submaximal swimming training for 12 weeks. The levels of IL-10 in homogenized lung tissue were measured by ELISA.Results:Findings indicated that a period of swimming training increased the IL-10 levels significantly in lung tissue of training group when compared to control (P=0.00) and NNK groups (P=0.00). Also, a significant increase of IL-10 level was observed in exercise + NNK group when compared to NNK group (p≤0/02). Furthermore, it was observed that IL-10 levels of NNK group had a significant decrease when compared to training group (P=0/00), training + NNK group (p≤0/02), but had insignificant increase when compared to saline group (p≤0/85).Conclusions:Generally, it could be confirmed that regular submaximal aerobic training plays an important role in the inhibition of the effects of lung inflammation induced by NNK via increasing IL-10 activity.

ATP serves an anti-inflammatory role by enhancing β-defensin-2 response in acute pneumonia of rat.

The aim of the current study was to evaluate the effect of ATP on the expression of rat β-defensin-2 (rBD-2) in a time-dependent manner, as well as its therapeutic value in an acute pneumonia rat model. A total of 30 rats as a treatment group and 30 as a control group were treated with the same dose of ATP and normal saline, respectively, lung tissues were isolated from rat and expression of rBD-2 mRNA was assessed with reverse transcription-quantitative polymerase chain reaction (RT-qPCR) at 12, 24 and 36 h following treatment. Rats were divided into five groups: The control group treated with normal saline, the Pseudomonas aeruginosa (PA) infected group, group treated with ATP, group treated with cephalosporins, and the group treated with both ATP and cephalosporins. At 24 h following treatment, rat serum and lung tissues were collected for assessment of histological changes, and alterations to expression of the rBD-2 protein by immunohistochemistry, expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6 proteins by ELISA. RT-qPCR results indicated that the expression of rBD-2 mRNA was upregulated in response to ATP stimulation in lung tissues of rat, reaching its highest peak at 24 h. Immunohistochemistry demonstrated that ATP treatment enhanced the expression of rBD-2 protein in rat lungs. Ceftazidime and ATP protected lungs from infection of PA and reduced the pathological damage of the lung. Overexpression of rBD-2 by ATP led to decreased protein expression of TNF-α and IL-6 in lung tissues and serum. ATP upregulates the expression of rBD-2 and serves an anti-inflammatory role in the acute pneumonia of a rat model.

Role of carbonyl sulfide in acute lung injury following limb ischemia/reperfusion in rats

ObjectiveTo investigate the effect of carbonyl sulfide (COS) on limb ischemia/reperfusion (I/R)-induced acute lung injury (ALI) and the associated mechanism in rats.MethodsALI was induced by bilateral hind limb I/R in Sprague–Dawley (SD) rats. Sixty-four SD rats were randomly divided into the control group, I/R group, I/R + COS group, and I/R + AIR group. We observed the survival rate of the rats and the morphological changes of lung tissues, and we measured the change in the lung coefficient, the expression levels of the intercellular adhesion factor-1 (ICAM-1) protein in lung tissue, the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-lβ, and interleukin (IL)-6 in both lung tissue and serum, and cell apoptosis.ResultsLimb I/R caused significant lung tissue damage. The number of polymorphonuclear neutrophil in alveolar septa, the expression level of the ICAM-1 protein in lung tissue, the expression levels of TNF-α, IL-1, and IL-6 in lung tissue and serum, the lung coefficient, and cell apoptosis all increased. When a low dose of COS gas was administered prior to limb I/R, the variation of the above indicators was significantly reduced, while an increase in the dose of COS did not reduce the lung injury but rather increased the mortality rate.ConclusionCarbonyl sulfide is another new gaseous signaling molecule, and a low dose of exogenous COS may play a protective role in I/R-induced ALI by acting as an anti-inflammatory agent by promoting the production of antioxidants and by inhibiting the expression of adhesion molecule proteins.

Phloretin Exerts Anti-Tuberculosis Activity and Suppresses Lung Inflammation.

An increase in the prevalence of the drug-resistant Mycobacteria tuberculosis necessitates developing new types of anti-tuberculosis drugs. Here, we found that phloretin, a naturally-occurring flavonoid, has anti-mycobacterial effects on H37Rv, multi-drug-, and extensively drug-resistant clinical isolates, with minimum inhibitory concentrations of 182 and 364 μM, respectively. Since Mycobacteria cause lung inflammation that contributes to tuberculosis pathogenesis, anti-inflammatory effects of phloretin in interferon-γ-stimulated MRC-5 human lung fibroblasts and lipopolysaccharide (LPS)-stimulated dendritic cells were investigated. The release of interleukin (IL)-1β, IL-12, and tumor necrosis factor (TNF)-α was inhibited by phloretin. The mRNA levels of IL-1β, IL-6, IL-12, TNF-α, and matrix metalloproteinase-1, as well as p38 mitogen-activated protein kinase and extracellular signal-regulated kinase phosphorylation, were suppressed. A mouse in vivo study of LPS-stimulated lung inflammation showed that phloretin effectively suppressed the levels of TNF-α, IL-1β, and IL-6 in lung tissue with low cytotoxicity. Phloretin was found to bind M. tuberculosis β-ketoacyl acyl carrier protein synthase III (mtKASIII) with high affinity (7.221 × 107 M−1); a binding model showed hydrogen bonding of A-ring 2′-hydroxy and B-ring 4-hydroxy groups of phloretin with Asn261 and Cys122 of mtKASIII, implying that mtKASIII can be a potential target protein. Therefore, phloretin can be a useful dietary natural product with anti-tuberculosis benefits.

Schistosoma mansoni Tegument (Smteg) Induces IL-10 and Modulates Experimental Airway Inflammation.

BackgroundPrevious studies have demonstrated that S. mansoni infection and inoculation of the parasite eggs and antigens are able to modulate airways inflammation induced by OVA in mice. This modulation was associated to an enhanced production of interleukin-10 and to an increased number of regulatory T cells. The S. mansoni schistosomulum is the first stage to come into contact with the host immune system and its tegument represents the host-parasite interface. The schistosomula tegument (Smteg) has never been studied in the context of modulation of inflammatory disorders, although immune evasion mechanisms take place in this phase of infection to guarantee the persistence of the parasite in the host.Methodology and Principal FindingsThe aim of this study was to evaluate the Smteg ability to modulate inflammation in an experimental airway inflammation model induced by OVA and to characterize the immune factors involved in this modulation. To achieve the objective, BALB/c mice were sensitized with ovalbumin (OVA) and then challenged with OVA aerosol after Smteg intraperitoneal inoculation. Protein extravasation and inflammatory cells were assessed in bronchoalveolar lavage and IgE levels were measured in serum. Additionally, lungs were excised for histopathological analyses, cytokine measurement and characterization of the cell populations. Inoculation with Smteg led to a reduction in the protein levels in bronchoalveolar lavage (BAL) and eosinophils in both BAL and lung tissue. In the lung tissue there was a reduction in inflammatory cells and collagen deposition as well as in IL-5, IL-13, IL-25 and CCL11 levels. Additionally, a decrease in specific anti-OVA IgE levels was observed. The reduction observed in these inflammatory parameters was associated with increased levels of IL-10 in lung tissues. Furthermore, Smteg/asthma mice showed high percentage of CD11b+F4/80+IL-10+ and CD11c+CD11b+IL-10+ cells in lungs.ConclusionTaken together, these findings demonstrate that S. mansoni schistosomula tegument can modulates experimental airway inflammation.

LFG-500, a newly synthesized flavonoid, attenuates lipopolysaccharide-induced acute lung injury and inflammation in mice

Acute lung injury (ALI) often causes significant morbidity and mortality worldwide. Improved treatment and effective strategies are still required for ALI patients. Our previous studies demonstrated that LFG-500, a novel synthesized flavonoid, has potent anti-cancer activities, while its anti-inflammatory effect has not been revealed. In the present study, the in vivo protective effect of LFG-500 on the amelioration of lipopolysaccharide (LPS)-induced ALI and inflammation was detected. LFG-500 attenuated LPS-induced histological alterations, suppressed the infiltration of inflammatory cells in lung tissues and bronchoalveolar lavage fluid, as well as inhibited the secretion of several inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 in lung tissues after LPS challenge. In addition, the in vitro effects and mechanisms were studied in LPS stimulated RAW 264.7 cells and THP-1 cells. LFG-500 significantly decreased the secretion and expression of TNF-α, IL-1β, and IL-6 through inhibiting the transcriptional activation of NF-κB. Moreover, overexpression of NF-κB p65 reversed the inhibitory effect of LFG-500 on LPS-induced NF-κB activation and inflammatory cytokine secretion. Further elucidation of the mechanism revealed that p38 and JNK MAPK pathways were involved in the anti-inflammation effect of LFG-500, through which LFG-500 inhibited the classical IKK-dependent pathway and led to inactivation of NF-κB. More importantly, LFG-500 suppressed the expression and nuclear localization of NF-κB in LPS-induced ALI mice. Taken together, these results demonstrated that LFG-500 could attenuate LPS-induced ALI and inflammation by suppressing NF-κB activation, which provides new evidence for the anti-inflammation activity of LFG-500.

Effect of compound Maqin decoction on TGF-β1/Smad proteins and IL-10 and IL-17 content in lung tissue of asthmatic rats.

In this research, compound Maqin decoction (CMD) has been shown to positively affect in airway inflammation of asthma models. We evaluated the effects of CMD on the expression of transforming growth factor (TGF)-β1/Smad proteins, interleukin (IL)-17, and IL-10 in lung tissue of asthmatic rats. Asthma was induced in a rat model using ovalbumin. After a 4-week treatment with CMD, rats were killed to evaluate the expression of TGF-β1 and Smad proteins in lung tissue. IL-10 and IL-17 levels in lung tissue homogenates were determined by ELISA. The expression of TGF-β1 and Smad3 protein increased, whereas expression of Smad7 protein decreased upon high-dose or low-dose treatment with CMD or by intervention with dexamethasone, compared to the control. There was a significant difference between treatment with a high dose CMD and the control treatment, but no significant difference was found between high-dose CMD treatment and dexamethasone intervention. The expression of TGF-β1 and Smad7 protein increased, whereas the expression of Smad3 protein decreased in the model group compared to other groups. In the CMD high-dose group, low-dose group, and dexamethasone intervention group, the IL-17 concentrations in lung tissue homogenates were decreased, while IL-10 levels were increased. Again, there was a significant difference between CMD high-dose and control treatment, but not between CMD high-dose treatment and dexamethasone intervention. Thus, positive effects of CMD against asthmatic airway remodeling may be due to its regulatory effect on TGF-β1, Smad3, and Smad7 protein levels and on cytokines such as IL-10 and IL-17.

Effects of sevoflurane on ventilator induced lung injury in a healthy lung experimental model

Introduction and objectiveVentilator-induced lung injury (VILI) causes a systemic inflammatory response in tissues, with an increase in IL-1, IL-6 and TNF-α in blood and tissues. Cytoprotective effects of sevoflurane in different experimental models are well known, and this protective effect can also be observed in VILI. The objective of this study was to assess the effects of sevoflurane in VILI. Material and methodsA prospective, randomized, controlled study was designed. Twenty female rats were studied. The animals were mechanically ventilated, without sevoflurane in the control group and sevoflurane 3% in the treated group (SEV group). VILI was induced applying a maximal inspiratory pressure of 35cmH2O for 20min without any positive end-expiratory pressure for 20min (INJURY time). The animals were then ventilated 30min with a maximal inspiratory pressure of 12cmH2O and 3cmH2O positive end-expiratory pressure (time 30min POST-INJURY), at which time the animals were euthanized and pathological and biomarkers studies were performed. Heart rate, invasive blood pressure, pH, PaO2, and PaCO2 were recorded. The lung wet-to-dry weight ratio was used as an index of lung edema. ResultsNo differences were found in the blood gas analysis parameters or heart rate between the 2 groups. Blood pressure was statistically higher in the control group, but still within the normal clinical range. The percentage of pulmonary edema and concentrations of TNF-α and IL-6 in lung tissue in the SEV group were lower than in the control group. ConclusionsSevoflurane attenuates VILI in a previous healthy lung in an experimental subclinical model in rats.

Efectos del sevoflurano en la lesión pulmonar inducida por la ventilación mecánica en un modelo experimental de pulmón sano

Introduction and objectiveVentilator-induced lung injury (VILI) causes a systemic inflammatory response in tissues, with an increase in IL-1, IL-6 and TNF-α in blood and tissues. Cytoprotective effects of sevoflurane in different experimental models are well known, and this protective effect can also be observed in VILI. The objective of this study was to assess the effects of sevoflurane in VILI. Material and methodsA prospective, randomized, controlled study was designed. Twenty female rats were studied. The animals were mechanically ventilated, without sevoflurane in the control group and sevoflurane 3% in the treated group (SEV group). VILI was induced applying a maximal inspiratory pressure of 35cmH2O for 20min without any positive end-expiratory pressure for 20min (INJURY time). The animals were then ventilated 30min with a maximal inspiratory pressure of 12cmH2O and 3cmH2O positive end-expiratory pressure (time 30min POST-INJURY), at which time the animals were euthanized and pathological and biomarkers studies were performed. Heart rate, invasive blood pressure, pH, PaO2, and PaCO2 were recorded. The lung wet-to-dry weight ratio was used as an index of lung edema. ResultsNo differences were found in the blood gas analysis parameters or heart rate between the 2 groups. Blood pressure was statistically higher in the control group, but still within the normal clinical range. The percentage of pulmonary edema and concentrations of TNF-α and IL-6 in lung tissue in the SEV group were lower than in the control group. ConclusionsSevoflurane attenuates VILI in a previous healthy lung in an experimental subclinical model in rats.

Dynamic alteration of spleen dendritic cells in acute lung injury mice

Objective To investigate the kinetics and phenotype of spleen dendritic cells (DC) in lipopolysaccharide (LPS) -induced acute lung injury (ALI) mice. Methods Thirty-six C57BL/6 mice were randomly (random number) divided into two groups: control group and ALI group. Spleens were harvested at the following intervals of 6, 12, and 24 h after LPS or PBS administration. Lung wet weight/body weight ratio (LW/BW) was recorded to assess lung injury. Meanwhile, pathological changes were examined under optical microscope. The IL-6 level in the lung was measured by using ELISA (enzyme-linked immuno sorbent assay) . The DC in the spleen was measured by flow cytometry (FCM) . Results (1) LPS-ALI resulted in a significant increase in LW/BW ratio. (2) Histologically, extensive alveolar wall thickening resulted from edema, severe hemorrhage in the interstitium and alveolus, and marked and diffuse interstitial infiltration with inflammatory cells were observed in the ALI group. (3) Meanwhile, the levels of IL-6 in lung tissue were significantly increased in the LPS-induced ALI mice. (4) LPS-induced ALI led to divergent kinetics of spleen DC in ALI mice. In ALI mice, spleen DC only showed a transient increase at 12 h. (5) All DC within spleens had a modest maturation in ALI mice. Conclusions LPS-induced ALI provokes a transient increase as well as modest maturation of spleen DC. Key words: Acute lung injury; Acuet respiratory distress syndrome; Dendritic cells; Spleen; Inflammation

Keratinocyte growth factor-2 is protective in lipopolysaccharide-induced acute lung injury in rats

Keratinocyte growth factor-2 (KGF-2) plays a key role in lung development, but its role in acute lung injury has not been well characterized. Lipopolysaccharide instillation caused acute lung injury, which significantly elevated lung wet-to-dry weight ratio, protein and neutrophils in bronchoalveolar lavage fluid (BALF), inhibited surfactant protein A and C expression in lung tissue, and increased pathological injury. Pretreatment with KGF-2 improved the above lung injury parameters, partially restored surfactant protein A and C expression, and KGF-2 given 2–3 days before LPS challenge showed maximum lung injury improvement. Pretreatment with KGF-2 also markedly reduced the levels of TNF-α, MIP-2, IL-1β and IL-6 in BALF and the levels of IL-1β and IL-6 in lung tissue. Histological analysis showed there was increased proliferation of alveolar type II epithelial cells in lung parenchyma, which reached maximal 2 days after KGF-2 instillation. Intratracheal administration of KGF-2 attenuates lung injury induced by LPS, suggesting KGF-2 may be potent in the intervention of acute lung injury.