Model Of Chronic Inflammation Research Articles

Raphanus sativus Seeds Oil Arrested in vivo Inflammation and Angiogenesis through Down-regulation of TNF-α.

Raphanus sativus is traditionally used as an anti-inflammatory agent. The current study was designed to explore the in vivo anti-inflammatory and antiangiogenic properties of Raphanus sativus seeds oil. Cold press method was used for the extraction of oil (RsSO) and was characterised by using GC-MS techniques. Three in vitro antioxidant assays (DPPH, ABTS and FRAP) were performed to explore the antioxidant potential of RsSO. Disc diffusion methods were used to study in vitro antimicrobial properties. In vivo anti-inflammatory properties were studied in both acute and chronic inflammation models. In vivo chicken chorioallantoic membrane assay was performed to study antiangiogenic effects. Molecular mechanisms were identified using TNF-α ELISA kit and docking tools. GC-MS analysis of RsSO revealed the presence of hexadecanoic and octadecanoic acid. Findings of DPPH, ABTS, and FRAP models indicated relatively moderate radical scavenging properties of RsSO. Oil showed antimicrobial activity against a variety of bacterial and fungal strains tested. Data of inflammation models showed significant (p < 0.05) anti-inflammatory effects of RsSO in both acute and chronic models. 500 mg/kg RsSO halted inflammation development significantly better (p < 0.05) as compared with lower doses. Histopathological evaluations of paws showed minimal infiltration of inflammatory cells in RsSO-treated animals. Findings of TNF-α ELSIA and docking studies showed that RsSO has the potential to down-regulate the expression of TNF-α, iNOS, ROS, and NF-κB respectively. Moreover, RsSO showed in vivo antiangiogenic effects. Data of the current study highlight that Raphanus sativus seeds oil has anti-inflammatory, and antiangiogenic properties and can be used as an adjunct to standard NSAIDs therapy which may reduce the dose and related side effects.

Increased ten-eleven translocation methylcytosine dioxygenase one in dorsal root ganglion contributes to inflammatory pain in CFA rats.

DNA hydroxylation catalyzed by Tet dioxygenases occurs abundantly in neurons in mammals. However, effects of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) expression and hydroxymethylation status on neuron injury remain unclear. This study was designed to explore the effects of TET1 and TET2 expression in the inflammatory pain of rats induced by complete Freund's adjuvant (CFA). Mechanical paw withdrawal threshold (PWT) and thermal withdrawal latency (TWL) were detected to assess pain behavior. The expression of TET1 and TET2 were measured in the dorsal root ganglion (DRG) with western blotting analysis. Immunofluorescence staining is employed to detect the expression and co-location of TRPV1 with TET1. Intrathecal administration of Bobcat339 was used to inhibit TET1 function in dorsal root ganglion. The paw withdrawal threshold and thermal withdrawal latency of rats were significantly reduced after CFA Injection. Western blot results showed that the expression of TET1 was significantly increased at 3days after CFA injection, but TET2 had no statistical difference. Immunofluorescence results showed that TET1 was co-localized with TRPV1. Intrathecal administration of Bobcat339 improved mechanical and thermal pain threshold in CFA rats. Our findings highlight the role of TET1 in chronic inflammatory pain model. The expression of TET1 was increased in CFA rats, and suppression of TET1 will ameliorate inflammatory pain.

Effects of administration of α2 adrenergic receptor agonist into psoas major muscle on inflammatory pain induced by injection of complete Freund’s adjuvant in rats

α2 adrenergic agonists are widely used in clinical anesthesia and ICU sedation owing to their effective sedative and analgesic effects. Lumbago and leg pain is the most common clinical pain disease. Studies have reported that lumbago and leg pain is associated with dysregulation of paravertebral muscles, especially psoas major muscles. In the present study, a unilateral lower extremity chronic inflammation and pain model was established by subcutaneous administration of low-dose complete Fredrin’s adjuvant (CFA) into the posterior paw of rats. α2 adrenalin receptor agonist was then injected into the psoas major muscle. Behavioral tests were conducted for 21 days. Psoas major muscle tissue was harvested for evaluation of biochemical indexes related to pain. The effect of α2 adrenergic receptor agonist injected into psoas major muscle on chronic inflammatory pain of lower extremities in rats was explored. The results showed that injection of α2 adrenergic receptor agonist into the psoas major muscle relieved CFA-induced mechanical hyperalgesia. Administration of α2 adrenergic receptor antagonist yohimbine reversed the analgesic effect of α2 adrenergic receptor agonists. Administration of dexmedetomidine into psoas major muscle downregulated the levels of norepinephrine, interleukin-6 and tumor necrosis factor-α in tissues. The findings of the present study show that administration of α2 adrenoceptor agonists into the psoas major muscle relieves chronic inflammatory pain induced by CFA. Local injection of dexmedetomidine also exerted anti-inflammatory and anti-sympathetic effect by activating α2-adrenoceptor in the psoas major muscle.

Gasdermin E mediates pyroptotic cell death of neutrophils and macrophages in a zebrafish model of chronic skin inflammation

Chronic diseases and hematopoietic disorders are associated with dysregulation of the inflammasome. Our group has recently reported the relevance of the inflammasome in the differentiation of hematopoietic stem and progenitor cells. However, the impact of the inflammasome of myeloid cells in the regulation of hematopoiesis is largely unknown. In this study, we used the unique advantages of the zebrafish model to demonstrate that genetic inhibition of macrophage inflammasome resulted in increased number of macrophages in larvae with skin inflammation without affecting erythrocyte and neutrophil counts. Similarly, the inhibition of the neutrophil inflammasome by the same strategy resulted in increased number of neutrophils in larvae with skin inflammation but did not affect erythrocytes and macrophages. Consistently, hyperactivation of the inflammasome in neutrophils in this model promoted neutrophil death, which was recovered by pharmacological inhibition of Gasdermin E. We conclude that the myeloid inflammasome autonomously regulates pyroptotic cell death in chronic inflammation through a Gasdermin E-dependent pathway in zebrafish.

Chronic facial inflammatory pain-induced anxiety is associated with bilateral deactivation of the rostral anterior cingulate cortex

Patients with chronic pain, especially orofacial pain, often suffer from affective disorders, including anxiety. Previous studies largely focused on the role of the caudal anterior cingulate cortex (cACC) in affective responses to pain, long-term potentiation (LTP) in cACC being thought to mediate the interaction between anxiety and chronic pain. But recent evidence indicates that the rostral ACC (rACC), too, is implicated in processing affective pain. However, whether such processing is associated with neuronal and/or synaptic plasticity is still unknown. We addressed this issue in a chronic facial inflammatory pain model (complete Freund's adjuvant model) in rats, by combining behavior, Fos protein immunochemistry and ex vivo intracellular recordings in rACC slices prepared from these animals. Facial mechanical allodynia occurs immediately after CFA injection, peaks at post-injection day 3 and progressively recovers until post-injection days 10–11, whereas anxiety is delayed, being present at post-injection day 10, when sensory hypersensitivity is relieved, but, notably, not at post-injection day 3. Fos expression reveals that neuronal activity follows a bi-phasic time course in bilateral rACC: first enhanced at post-injection day 3, it gets strongly depressed at post-injection day 10. Ex vivo recordings from lamina V pyramidal neurons, the rACC projecting neurons, show that both their intrinsic excitability and excitatory synaptic inputs have undergone long-term depression (LTD) at post-injection day 10. Thus chronic pain processing is associated with dynamic changes in rACC activity: first enhanced and subsequently decreased, at the time of anxiety-like behavior. Chronic pain-induced anxiety might thus result from a rACC deactivation-cACC hyperactivation interplay.

Nanoencapsulation of Bimi® extracts increases its bioaccessibility after in vitro digestion and evaluation of its activity in hepatocyte metabolism

Isothiocyanates (ITCs) have low stability in aqueous conditions, reducing their bioavailability when used as food ingredients. Therefore, the aim of this work was to increase the stability of the ITCs present in extracts of Bimi® edible parts by nanoencapsulation using cauliflower-derived plasma membrane vesicles. The bioactivity of these nanoencapsulates was evaluated in a HepG2 hepatocyte cell line in a model for low-grade chronic inflammation. The vesicles showed a higher capacity of retention in the in vitro gastrointestinal digestion for 3,3-diindolylmethane (DIM), indole-3-carbinol (I3C) and sulforaphane (SFN). Furthermore, Transmission Electron Microscopy (TEM) analysis of the vesicles revealed a decreased size under acidic pH and a release of their cargo after the intestinal digestion. The HepG2 experiments revealed differences in metabolism under the condition of chronic inflammation. The cauliflower-derived plasma membrane vesicles are able to enhance the stability of ITCs through the in vitro gastrointestinal digestion, improving their bioaccesibility and potential bioavailability.

Evaluation of Anti-bacterial and Anti-inflammatory Activities of Ethanolic Extract of Hibiscus hirtus Linn. Leaves

The current investigation is started to find the antibacterial and anti-inflammatory activities of the sub shrub Hibiscus hirtus L. The leaves of this conventional shrub were found to possess' different activities which incorporate antibacterial and hostile to helminthic effects. Thus we made an endeavor to perform extraction utilizing ethanol as solvent and soxhlation as a strategy for extraction. The leaves were priorly researched for their pharmacognostic, phytochemical and physical parameters. The antibacterial action of the ethanolic leaf extract was conveyed at various concentrations on strains of gram positive and gram-negative bacteria, for example, Staphylococcus aureus and Escherechia coli individually by utilizing cup and plate technique. The outcomes were outfitted as the zone of inbition acquired around every grouping of the concentrate and were compared with those of standard antibiotic utilized in the analysis, amoxycillin. Anti-inflammatory activity of Hibiscus hirtus L was studied and compared with standard drug, ibuprofen. Ethanollic concentrate of leaves (2.5-15 mg/ml) and ibuprofen (2.5-15 mg/ml) were utilized to measure the paw edema by plethysmometer and compared with control groups. Hibiscus hirtus L showed critical decrease of paw edema in the chosen model of inflammation for example formalin prompted chronic model of inflammation. Ethanollic concentrate of the plant leaves showed anti- microbial and anti-inflammatory impacts.

STAT6 Blockade Abrogates Aspergillus-Induced Eosinophilic Chronic Rhinosinusitis and Asthma, A Model of Unified Airway Disease.

Unified airway disease, including concurrent asthma and chronic rhinosinusitis (CRS), is a common, but poorly understood disorder with no curative treatment options. To establish a murine model of chronic unified eosinophilic airway inflammation, mice were challenged with Aspergillus niger, and sinonasal mucosa and lung tissue were evaluated by immunohistochemistry, flow cytometry, and gene expression. Inhalation of A niger conidia resulted in a Th2-biased lung and sinus inflammation that typifies allergic asthma and CRS. Gene network and pathway analysis correlated with human disease with upregulation of not only the JAK-STAT and helper T-cell pathways, but also less expected pathways governing the spliceosome, osteoclast differentiation, and coagulation pathways. Utilizing a specific inhibitor and gene-deficient mice, we demonstrate that STAT6 is required for mycosis-induced sinus inflammation. These findings confirm the relevance of this new model and portend future studies that further extend our understanding of the immunopathologic basis of airway mycosis and unified airway disease.

Interfering with alternatively activated macrophages by CSF-1R inhibition exerts therapeutic capacity on allergic airway inflammation

PurposeAllergic asthma is a chronic inflammatory disorder with airway hyperresponsiveness and tissue remodeling as the main pathological characteristics. The etiology of asthma is relatively complicated, involving genetic susceptibility, epigenetic regulation, environmental factors, and immune imbalance. Colony stimulating factor 1 receptor (CSF-1R), highly expressed in myeloid monocytes, plays an important role in regulating inflammation. However, the pathological role of CSF-1R and the therapeutic effects of CSF-1R inhibitor in allergic airway inflammation remain indistinct. MethodsThe house dust mite (HDM)-triggered allergic airway inflammation model was conducted to fully uncover the efficacies of CSF-1R inhibition, as illustrated by histopathological examinations, biochemical analysis, ELISA, RT-PCR, Western blotting assay, immunofluorescence, and flow cytometry. Furthermore, bone marrow-derived macrophages (BMDMs) were differentiated and polarized upon IL-4/IL-13 induction to clarify the underlying mechanisms of CSF-1R inhibition. ResultsHerein, we presented that the expression of CSF-1R was increased in HDM-induced experimental asthma and inhibition of CSF-1R displayed dramatic effects on the disease severity of asthma, referring to suppressing the secretion of allergic mediators, dysfunction of airway epithelium, and infiltration of inflammatory cells. Furthermore, CSF-1R inhibitor could markedly restrain the polarization and expression of transcriptional factors of alternatively activated macrophages (AAMs) in the presence of IL-4/IL-13 and reduce the recruitment of CSF-1R-dominant macrophages, both in acute and chronic allergic airway inflammation model. ConclusionCollectively, our findings demonstrated the molecular pathological mechanism of CSF-1R in allergic airway diseases and suggested that targeting CSF-1R might be an alternative intervention strategy on the homeostasis of airway immune microenvironment in asthma.

Evidence of Anti-Inflammatory Effect of Transcranial Direct Current Stimulation in a CFA-Induced Chronic Inflammatory Pain Model in Wistar Rats

Introduction: Given that chronic inflammatory pain is highly prevalent worldwide, it is important to study new techniques to treat or relieve this type of pain. The present study evaluated the effect of transcranial direct current stimulation (tDCS) in rats submitted to a chronic inflammatory model by nociceptive response, biomarker levels (brain-derived neurotrophic factor [BDNF] and interleukin [IL]-6 and IL-10), and by histological parameters. Methods: Sixty-day-old male Wistar rats were used in this study and randomized by weight into 6 major groups: total control, control + sham-tDCS, control + active tDCS, total CFA, CFA + sham-tDCS, and CFA + active tDCS. After inflammatory pain was established, the animals were submitted to the treatment protocol for 8 consecutive days, according to the experimental group. The nociceptive tests (von Frey and hot plate) were assessed, and euthanasia by decapitation occurred at day 8 after the end of tDCS treatment, and the blood serum and central nervous structures were collected for BDNF and IL measurements. All experiments and procedures were approved by the Institutional Committee for Animal Care and Use (UFPel #4538). Results: The tDCS treatment showed a complete reversal of the mechanical allodynia induced by the pain model 24 h and 8 days after the last tDCS session, and there was partial reversal of the thermal hyperalgesia at all time points. Serum BDNF levels were decreased in CFA + sham-tDCS and CFA + tDCS groups compared to the control + tDCS group. The control group submitted to tDCS exhibited an increase in serum IL-6 levels in relation to the other groups. In addition, there was a significant decrease in IL-10 striatum levels in control + tDCS, CFA, and CFA + sham-tDCS groups in relation to the control group, with a partial tDCS effect on the CFA pain model. Local histology demonstrated tDCS effects in decreasing lymphocytic infiltration and neovascularization and tissue regeneration in animals exposed to CFA. Conclusion: tDCS was able to reverse the mechanical allodynia and decrease thermal hyperalgesia and local inflammation in a chronic inflammatory pain model, with a modest effect on striatum IL-10 levels. As such, we suggest that analgesic tDCS mechanisms may be related to tissue repair by modulating the local inflammatory process.

Effects of dexamethasone and acetylsalicylic acid on inflammation caused by Complete Freund's adjuvant in the naked mole rat (Heterocephalus glaber)

The naked mole rat (NMR) is a fossorial rodent that has been observed to have a unique nociceptive system in comparison to others. In this study, we explored on characterization of chronic inflammation in the NMR using Complete Freund's adjuvant (CFA) and investigated the effects of dexamethasone and acetylsalicylic acid on the resulting inflammation. The NMRs were injected with 0.1 ml of CFA subcutaneously in the right hind paw, and an equivalent volume of normal saline was injected to the control group. Swelling of the injected right hind limb was observed within 24 h of injection, which involved the tibiotarsal joint, palmar surface and the digits of the injected paw. Swelling persisted for 6 weeks of experimentation and peaked between day 14 and 21. The resulting inflammation affected the mobility, stance and joint rigidity of CFA treated NMRs in comparison to the control group. Treatment of the chronic phase of the inflammation from the 11th day with dexamethasone and acetylsalicylic acid showed no statistical significance in paw circumference compared to the control group, other than on a few, negligible occasions. The present data showed that CFA was able to induce chronic inflammation in the NMR, and the NMR could thus be established as a model for chronic inflammation. There is, however, need for more sensitive parameters to evaluate the effects of anti-inflammatory drugs.

Further evidence to support acute and chronic anti-inflammatory effects of Nasturtium officinale.

Background and purpose:Previously, we reported the anti-inflammatory properties of Nasturtium officinale (watercress) in several models of acute inflammation. This study was designed to explore the effects of topical and systemic administrations of N. officinale in the two chronic inflammatory models and to evaluate the role of TNF-α and IL-1β in these effects.Experimental approach:Folin-Ciocalteu and aluminum chloride methods were used to estimate the extract’s total phenol and flavonoid content, respectively. Carrageenan-induced paw edema was carried out and TNF-α and IL-1β concentrations in the carrageenan-treated paw tissue were determined. Formalin injection into rat hind paws (7 days) and the application of 12-O-tetradecanoyl phorbol-13-acetate (TPA) on mouse ears (9 days) were used to simulate chronic inflammation. Furthermore, a histological assessment of the inflamed tissues was carried out.Findings/Results:The extract’s flavonoid and phenolic contents were 90.26 ± 4.81 mg rutin equivalents/g and 68 ± 8.16 gallic acid equivalents/g gallic acid, respectively. N. officinale pretreatment in all doses administered considerably decreased carrageenan-induced edema. The extract also reduced IL-1β levels in carrageenan- treated paws while did not affect TNF-α levels. Oral and topical administrations of N. officinale considerably reserved the paw and ear edema. The extract also ameliorated the tissue injuries due to formalin and TPA challenges.Conclusion and implications:The data confirmed the topical and systemic anti-inflammatory effects of watercress against two chronic models of inflammation. They suggested that these properties are not related to TNF-α but could be attributed to inhibition of IL-1β and inhibition of leukocyte infiltration.

Saffron extract (Safr'Inside™) improves anxiety related behaviour in a mouse model of low-grade inflammation through the modulation of the microbiota and gut derived metabolites.

Treatment of anxiety and depression predominantly centres around pharmacological interventions, which have faced criticism for their associated side effects, lack of efficacy and low tolerability. Saffron, which is reportedly well tolerated in humans, has been recognised for its antidepressant and anti-anxiety properties. Indeed, we previously reported upon the efficacy of saffron extract supplementation in healthy adults with subclinical anxiety. However, the molecular aetiology remains unclear. In a rodent model of low-grade chronic inflammation, we explored the impact of a saffron extract (Safr'Inside™) supplemented at a physiological dose, which equated to 22 ± 1.2 mg per day human equivalent dose for a person of 60 kg. Behavioural tests (Open Field task, Y maze, Novel object recognition), caecal 16S rRNA microbial sequencing, caecal 1H NMR metabolomic analysis and 2DE brain proteomic analyses were completed to probe gut-brain axis interactions. Time occupying the centre of the Open Field maze (OF) was increased by 62% in saffron supplemented animals. This improvement in anxiety-related behaviour coincided with gut microbial shifts, notably Akkermansia, Muribaculaceae, Christensenellacae and Alloprevotella which significantly increased in response to saffron supplementation. Akkermansia and Muribaculaceae abundance negatively correlated with the neurotoxic metabolite dimethylamine which was reduced in saffron supplemented animals. Brain proteomic analysis highlighted several significantly altered proteins including ketimine reductase mu-crystallin which also correlated with dimethylamine concentration. Both dimethylamine and ketimine reductase mu-crystallin were associated with OF performance. This may be indicative of a novel interaction across the gut-brain axis which contributes to anxiety-related disorders.

Microvesicles are released from microglia in mouse models of both peripheral acute inflammation and chronic skin inflammation.

Microvesicles are released from microglia in mouse models of both peripheral acute inflammation and chronic skin inflammation.

A Review on Potential Anti-Inflammatory Activity of Some Medicinal Plants in Animal Model

Inflammation is a protective response that develops against tissue injury and infection. Chronic inflammation, on the other hand, is the root cause of the pathogenesis of many inflammatory disorders, including cancer. The currently available anti-inflammatory drug therapy is often not successful or causes intolerable side effects. Therefore, the search for anti-inflammatory drugs without side effects has become a dream and ongoing effort of the Pharma companies. The concept and treatment of inflammation are described under Shotha and Shwayathu Chikitsa in Ayurveda. The concept of ama explains the pathogenesis of chronic inflammation. This review includes the anti-inflammatory activity of some medicinal plants in acute and chronic inflammatory animal models. Data were collected from existing articles on anti-inflammatory studies from various search engines. Here, a brief overview of some medicinal plants having anti-inflammatory activity along with their doses, used part extract, used animal model, and the result is provided. In this review, it was found that the majority of the selected plants have more or similar effects in comparison to standard drugs, indicating that medicinal plants have significant anti-inflammatory potential. This overview will attract the interest of investigators aiming at the design of novel therapeutic approaches for the treatment of various inflammatory conditions.

Pharmacological Investigation of Cassia hirsuta Seed Extract for its Anti-inflammatory Activity in Acute and Chronic Inflammatory Animal Models

Objective The declared goal of this research was to investigate anti-inflammatory and anti-arthritic effectiveness of ethanolic extract of Cassia hirsuta seeds EECH in animals employing Carrageenan-induced paw CIP edema and Complete Freundrsquos adjuvant CFA induced arthritis models.Methodology The seeds of Cassia hirsuta were collected shade dried extracted using ethanol in Soxhlet extractor and the extract was tested for phytochemicals and acute oral toxicity 423 - OECD guidelines. CIP edema was examined to ascertain anti-inflammatory property. The anti-arthritic activity of CFA was analyzed by measuring paw volume arthritic index and body weight. Hematological parameters and markers in serum levels of enzymes like SGPT SGOT serum RF and histopathological studies were also performed.Results The seed extract possessed various phytoconstituents like alkaloids flavonoids terpenoids phenols and tannins as active constituents. In acute oral toxicity study the EECH produced no lethality with maximum dose of up to 2000 mgkg bw. Hence 120th 110th amp 15th mgkg b.w were taken as lower moderate and higher dose respectively. EECH at concentration of 100 200 amp 400 mgkg was able to reduce the inflammation induced by carrageenan in rats. However 200 mgkg 400 mgkg has shown significant inhibition of arthritis in rats when challenged with CFA 0.1 mL. The EECH of dose 200 mgkg 400 mgkg had maintained normal architecture of bone normal areolar synovium and normal histology in comparison to arthritis control.Conclusion According to our findings the EECH demonstrated anti-oxidant anti-inflammatory amp antiarthritic activity in a dose-dependent manner. The phytoconstituents like flavonoids terpenoids and phenols as active constituents in the extract may justify its activity.nbsp

Anti-inflammatory Activity of Chlorella vulgaris in Experimental models of Rats

Background: The aim of present study is to evaluate the anti-inflmmatory activity of Chlorella vulgaris in acute and chronic experimental inflammatory model. Plant extract was analyzed for photochemical screening of different phytoconstituents. Methods: Paw edema was induced with 1.5% carrageenan to all the groups except normal. Diclofenac was used as a standard drug and Chlorella vulgaris at 50, 100, 200 mg/kg dose was used for study. Carrageenan was administered in the paw. Paw thickness was measured at 0, 1, 2 and 4 hr. Inflammatory cytokines and oxidative stress were measured in paw homogenate. Chronic inflammatory activity was screened by using cotton pellet induced granuloma. Results: In result, paw thickness was increased from 1 hr to 4 hr and Chlorella vulgaris treated group shows decrease in paw thickness. SOD and GSH content was decreased and MDA level increased in carrageenan injected group, however treatment groups shows reverse effects also we found that increase in cytokine level in carrageenan group and decrease in treatment group. In, egg albumin model paw volume was decreased in rats treated with Chlorella vulgaris. In chronic model CV treated group also showed dose dependent activity. Conclusion: From this study we conclude that Chlorella vulgaris has antiinflammatory activity.

Myeloid ABCG1 Deficiency Enhances Apoptosis and Initiates Efferocytosis in Bronchoalveolar Lavage Cells of Murine Multi-Walled Carbon Nanotube-Induced Granuloma Model.

The use of carbon nanotubes has increased in the past few decades. Carbon nanotubes are implicated in the pathogenesis of pulmonary sarcoidosis, a chronic granulomatous inflammatory condition. We developed a murine model of chronic granulomatous inflammation using multiwall carbon nanotubes (MWCNT) to investigate mechanisms of granuloma formation. Using this model, we demonstrated that myeloid deficiency of ATP-binding cassette (ABC) cholesterol transporter (ABCG1) promotes granuloma formation and fibrosis with MWCNT instillation; however, the mechanism remains unclear. Our previous studies showed that MWCNT induced apoptosis in bronchoalveolar lavage (BAL) cells of wild-type (C57BL/6) mice. Given that continual apoptosis causes persistent severe lung inflammation, we hypothesized that ABCG1 deficiency would increase MWCNT-induced apoptosis thereby promoting granulomatous inflammation and fibrosis. To test our hypothesis, we utilized myeloid-specific ABCG1 knockout (ABCG1 KO) mice. Our results demonstrate that MWCNT instillation enhances pulmonary fibrosis in ABCG1 KO mice compared to wild-type controls. Enhanced fibrosis is indicated by increased trichrome staining and transforming growth factor-beta (TGF-β) expression in lungs, together with an increased expression of TGF-β related signaling molecules, interleukin-13 (IL-13) and Smad-3. MWCNT induced more apoptosis in BAL cells of ABCG1 KO mice. Initiation of apoptosis is most likely mediated by the extrinsic pathway since caspase 8 activity and Fas expression are significantly higher in MWCNT instilled ABCG1 KO mice compared to the wild type. In addition, TUNEL staining shows that ABCG1 KO mice instilled with MWCNT have a higher percentage of TUNEL positive BAL cells and more efferocytosis than the WT control. Furthermore, BAL cells of ABCG1 KO mice instilled with MWCNT exhibit an increase in efferocytosis markers, milk fat globule-EGF factor 8 (MFG-E8) and integrin β3. Therefore, our observations suggest that ABCG1 deficiency promotes pulmonary fibrosis by MWCNT, and this effect may be due to an increase in apoptosis and efferocytosis in BAL cells.

Losartan Mitigates Oxidative Stress in the Brains of Aged IL10-/- Mice

Abstract Chronic inflammation has been linked to frailty and declined cognition in older adults. Activation of the renin-angiotensin system (RAS) through the angiotensin Type1 receptor (AT1R) has been suggested as a contributory factor that links both inflammation and aging. Here we examined the impact of 4 weeks of oral Losartan treatment on IL10-/- mice brains, a mouse model of chronic inflammation and frailty. Frontal cortex, cerebellar, and hippocampal tissue of aged (100 weeks old) male IL10-/- mice were studied. Western blot techniques were employed to quantify changes in brain AT1R, nitrotyrosine (NT) as an oxidative stress marker, and Tau proteins. Our data show that aged IL-10 mice have significantly higher levels of AT1R in the cortex tissue but not in cerebellar or hippocampal tissue compared to age and sex-matched WT mice (0.63 + 0.35 vs 1.5 + 0.54, WT vs IL10, respectively, P&amp;lt;0.004). When treated with LOS, brain cortical tissue of IL10 -/- mice showed significant decreases in levels of AT1R (1.5 + 0.54 vs 0.98 + 0.50, IL10 vs LOS treated IL10, respectively, P&amp;lt;0.04), NT (0.72 + 0.12 vs 0.42 + 0.10, IL10 vs LOS treated IL10, respectively, P&amp;lt;0.009), and Tau protein (1.3 + 0.31 vs 0.15 + 0.08, IL10 vs LOS treated IL10, respectively, P&amp;lt;0.004) as compared to control IL10-/- mice. Losartan treatment had no significant effect on hippocampal AT1R or NT levels. Our results highlight the impact of Losartan, a drug commonly prescribed for the treatment of high blood pressure, on the brain-specific angiotensin system and its downstream effects on brain oxidative stress and Tau pathology.

Restoring Oat Nanoparticles Mediated Brain Memory Function of Mice Fed Alcohol by Sorting Inflammatory Dectin-1 Complex Into Microglial Exosomes.

Microglia modulate pro-inflammatory and neurotoxic activities. Edible plant-derived factors improve brain function. Current knowledge of the molecular interactions between edible plant-derived factors and the microglial cell is limited. Here an alcohol-induced chronic brain inflammation model is used to identify that the microglial cell is the novel target of oat nanoparticles (oatN). Oral administration of oatN inhibits brain inflammation and improves brain memory function of mice that are fed alcohol. Mechanistically, ethanol activates dectin-1 mediated inflammatory pathway. OatN is taken up by microglial cells via β-glucan mediated binding to microglial hippocalcin (HPCA) whereas oatN digalactosyldiacylglycerol (DGDG) prevents assess of oatN β-glucan to dectin-1. Subsequently endocytosed β-glucan/HPCA is recruited in an endosomal recycling compartment (ERC) via interaction with Rab11a. This complex then sequesters the dectin-1 in the ERC in an oatN β-glucan dependent manner and alters the location of dectin-1 from Golgi to early endosomes and lysosomes and increases exportation of dectin-1 into exosomes in an Rab11a dependent manner. Collectively, these cascading actions lead to preventing the activation of the alcoholic induced brain inflammation signing pathway(s). This coordinated assembling of the HPCA/Rab11a/dectin-1 complex by oral administration of oatN may contribute to the prevention of brain inflammation.