Expression Levels Of Monocyte Chemoattractant Protein-1 Research Articles

Protective effect of modified Huangqi Chifeng decoction on immunoglobulin A nephropathy through toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-kappa B signaling pathway.

To examine the nephroprotective mechanism of modified Huangqi Chifeng decoction (, MHCD) in immunoglobulin A nephropathy (IgAN) rats. To establish the IgAN rat model, the bovine serum albumin, lipopolysaccharide, and carbon tetrachloride 4 method was employed. The rats were then randomly assigned to the control, model, telmisartan, and high-, medium-, and low-dose MHCD groups, and were administered the respective treatments via intragastric administration for 8 weeks. The levels of 24-h urinary protein, serum creatinine (CRE), and blood urea nitrogen (BUN) were measured in each group. Pathological alterations were detected. IgA deposition was visualized through the use of immunofluorescence staining. The ultrastructure of the kidney was observed using a transmission electron microscope. The expression levels of interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor-β1 (TGF-β1) were examined by immunohistochemistry and quantitative polymerase chain reaction. Levels of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor-kappa B (NF-κB) P65, were examined by immunohistochemistry, Western blotting, and quantitative polymerase chain reaction. The 24-h urine protein level in each group increased significantly at week 6, and worsen from then on. But this process can be reversed by treatments of telmisartan, and high-, medium-, and low-dose of MHCD, and these treatments did not affect renal function. Telmisartan, and high-, and medium-dose of MHCD reduced IgA deposition. Renal histopathology demonstrated the protective effect of high-, medium-, and low-dose of MHCD against kidney injury. The expression levels of MCP-1, IL-6, and TGF-β1 in kidney tissues were downregulated by low, medium and high doses of MHCD treatment. Additionally, treatment of low, medium and high doses of MHCD decreased the protein and mRNA levels of TLR4, MyD88, and NF-κB. MHCD exerted nephroprotective effects on IgAN rats, and MHCD regulated the expressions of key targets in TLR4/MyD88/NF-κB signaling pathway, thereby alleviating renal inflammation by inhibiting MCP-1, IL-6 expressions, and ameliorating renal fibrosis by inhibiting TGF-β1 expression.

Evaluation of Chemokines and Cytokines as Biomarkers for Disease Severity in COVID-19-Infected Patients

Background: Alterations in cytokine and chemokine levels during SARS-CoV-2 infection may serve as indicators of disease severity. Objectives: This study aimed to evaluate the levels of plasma cytokines and chemokines in patients with COVID-19. Methods: The study included 120 COVID-19 patients, divided into severe, mild, and recovered categories (n = 40 for each group). Plasma levels of cytokines such as interleukin 8 (IL-8) and tumor necrosis factor α (TNF-α) were measured using ELISA, while chemokines like monocyte chemoattractant protein 1 (MCP-1) and programmed death protein 1 (PD-1) were quantified through qRT-PCR. Results: A higher incidence of positive biomarkers IL-8, TNF-α, MCP-1, and PD-1 was observed in the severe group compared to the mild and recovered groups. Notably, the expression levels of PD-1 and MCP-1 were significantly elevated in severely infected individuals relative to those in healthy subjects. A strong positive correlation was also noted between PD-1 and MCP-1 levels in cases of severe infection. Conclusions: The findings suggest that MCP-1, PD-1, TNF-α, and IL-8 could act as biomarkers for assessing the severity of COVID-19 infections. These results aim to deepen our understanding of the immunopathological mechanisms at play in this disease.

Inhibition of Experimental Corneal Neovascularization by the Tight Junction Protein ZO-1.

Purpose: To explore the effects of the tight junction protein zonula occludens 1 (ZO-1) on experimental corneal neovascularization (CNV). Methods: CNV models were established in the left eyes of BALB/c mice using NaOH. Anti-ZO-1 neutralizing antibody was topically applied to the burnt corneas after modeling thrice a day for 1 week. CD31 expression was analyzed to calculate the ratio of CNV number to area using a corneal whole-mount fluorescent immunohistochemical assay. Messenger ribonucleic acid (mRNA) and protein expression levels of ZO-1, vascular endothelial growth factor (VEGF), interleukin (IL)-1β, IL-6, IL-8, IL-18, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor alpha (TNF-α), phosphorylated protein kinase C (pPKC), and clusterin in burned corneas were detected by reverse transcriptase polymerase chain reaction (PCR) and western blot analyses. Infiltration of neutrophils, macrophages, and progenitor cells was examined by flow cytometry. Results: CNV was obviously greater in 45 s than in 15 s alkali injury group. In another experiment, CNV was obviously greater in the ZO-1 antibody group than in the vehicle-treated group. Corneal mRNA and protein expression levels of VEGF, IL-1β, IL-6, IL-8, IL-18, and MCP-1 were significantly higher in the ZO-1 antibody group than in the control group. Infiltration of neutrophils, macrophages, and progenitor cells was significantly greater in the ZO-1 antibody group than in the control group. TNF-α expression was much higher in 45 s than in 15 s alkali injury group. However, protein expression of pPKC and clusterin was much lower in 45 s than in 15 s alkali injury group. Conclusions: Anti-ZO-1 neutralizing antibody-treated mice exhibited enhanced alkali-induced CNV through enhanced intracorneal infiltration of progenitor and inflammatory cells.

Trans-Chalcone protects male rats against high-fat emulsion-induced pancreatic injury by inhibiting TNF-α and MCP-1 expression

Background. High-fat diet (HFD) intake is linked to ectopic fat deposition in the pancreas. It also causes pancreatic inflammatory lesions. trans-Chalcone is a simple chalcone with protective effects against HFD-induced metabolic disorders. This study, for the first time, explored the possible effects of this chalcone on high-fat emulsion-induced pancreatic abnormalities in rats. Methods. Twenty-one male rats were randomly assigned into three groups: control (received 10% tween 80); HFD (received high-fat emulsion + 10% tween 80); and HFD + chalcone (received high-fat emulsion + trans-chalcone). Real-time PCR was used to assess pancreatic mRNA expression levels of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor α (TNF-α) in the pancreas of all rats. Results. High-fat emulsion increased the mRNA expression levels of inflammatory biomarkers, including TNF-α and MCP-1 in the pancreas of rats, and treatment with trans-chalcone prevented these high-fat emulsion-induced changes. Conclusion. trans-Chalcone can protect the pancreas of male rats against HFD-induced abnormalities through its anti-inflammatory effects. Practical Implications. It seems that consumption of HFD up-regulates the production of inflammatory mediators in the pancreas. On the other hand, trans-chalcone can ameliorate HFD-related pancreatic inflammation.

Comparison of cytokine levels in prostatic secretion between the IIIa and IIIb subtypes of prostatitis.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), also known as National Institutes of Health (NIH) type III prostatitis, is a common disorder with an unclear etiology and no known curative treatments. Based on the presence or absence of leukocytes in expressed prostatic secretion (EPS), CP/CPPS is classified further into IIIa (inflammatory) and IIIb (noninflammatory) subtypes. However, the severity of symptoms is not entirely consistent with the white blood cell (WBC) count. Following the preliminary finding of a link between inflammatory cytokines and CP/CPPS, we performed this clinical study with the aim of identifying cytokines that are differentially expressed according to whether the prostatitis subtype is IIIa or IIIb. We found that granulocyte colony-stimulating factor (G-CSF), interleukin-18 (IL-18), and monocyte chemoattractant protein-1 (MCP-1) levels were significantly elevated and interferon-inducible protein-10 (IP-10) and platelet-derived growth factor-BB (PDGF-BB) levels were downregulated in the EPS of patients with type IIIa prostatitis. In a word, it is a meaningful study in which we investigate the levels of various cytokines in EPS according to whether prostatitis is the IIIa or IIIb subtype. The combination of G-CSF, IL-18, MCP-1, IP-10, and PDGF-BB expression levels could form a basis for classification, diagnosis, and therapeutic targets in clinical CP/CPPS.

Correlation analysis of monocyte chemoattractant protein-1 and clinical characteristics and cognitive impairment in type 2 diabetes mellitus comorbid major depressive disorder.

Type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD) are both chronic diseases, and they are often co-morbid. Usually, T2DM and MDD are associated with cognitive impairment, and the comorbidity status of both may increase the risk of cognitive impairment, but the underlying pathogenesis is not clear. Studies have shown that inflammation, especially monocyte chemoattractant protein-1 (MCP-1), could be associated with the pathogenesis of type 2 diabetes mellitus comorbid major depressive disorder. To investigate the correlations of MCP-1 with clinical characteristics and cognitive impairment in type 2 diabetes mellitus patients combined with major depressive disorder. A total of 84 participants were recruited in this study, including 24 healthy controls (HC), 21 T2DM patients, 23 MDD patients, and 16 T2DM combined with MDD (TD) patients, to measure the serum MCP-1 levels using Enzyme-linked Immunosorbent Assay (ELISA). And the cognitive function, depression, and anxiety degree were assessed using Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), 17-item Hamilton Depression Scale (HAMD-17), and Hamilton Anxiety Scale (HAMA), respectively. (1) Serum MCP-1 expression levels in the TD group were higher than HC, T2DM, and MDD groups, respectively (p < 0.05). And compared with HC and MDD groups, serum MCP-1 levels in the T2DM group were higher (p < 0.05) statistically. Receiver Operating Characteristic (ROC) curve showed that MCP-1 could diagnose T2DM at cut-off values of 503.8 pg./mL (sensitivity 80.95%, specificity 79.17%, AUC = 0.7956) and of 718.1 pg./mL for TD (sensitivity 81.25%, specificity 91.67%, AUC = 0.9271). (2) Group differences in cognitive function were significant. Compared with the HC group, total RBANS scores, attention scores, and language scores in the TD group were lower, respectively (p < 0.05), and total RBANS scores, attention scores, and visuospatial/constructional scores in the MDD group were lower, respectively (p < 0.05). Compared with the T2DM group, immediate memory scores in HC, MDD, and TD groups were lower, respectively, and total RBANS scores in TD were lower (p < 0.05). (3) Correlation analysis showed that hip circumference was negatively correlated with MCP-1 levels in the T2DM group (R = -0.483, p = 0.027), but the correlation disappeared after adjusting age and gender (r = -0.372; p = 0.117), and there were no significant correlations between MCP-1 and other variables. MCP-1 may be involved in the pathophysiology of type 2 diabetes mellitus patients combined with major depressive disorder. And MCP-1 may be significant for the early evaluation and diagnosis of TD in the future.

Transplantation of olfactory ensheathing cells decreases local and serological monocyte chemoattractant protein 1 level during the acute phase of rat spinal cord injury.

Monocyte chemoattractant protein 1 (MCP1) is one of the most upregulated cytokines in the spinal cord and serum throughout acute spinal cord injury (SCI). Olfactory ensheathing cells (OECs) transplantation improves SCI through multiple mechanisms, including immunomodulation. Our study aimed to investigate whether OECs ameliorate acute inflammation after SCI by modulating MCP1 expression. We established a standardized clinically relevant contusion model using the NYU impactor. OECs were administered to the injured spinal cord via microinjection 30 minutes after injury. Rat locomotor functions were assessed by the Basso-Beattie-Bresnahan scale score. Time-course histopathological (H&E and IHC) analyses were performed to record rapid changes in acute inflammation at lesion epicenters. Serum MCP1 level was detected by ELISA assay. BBB scores showed improved locomotor functional recoveries in the OECs transplantation group after SCI ( P < 0.05). Staining of H&E and CD68 illustrated that OECs transplantation attenuated inflammatory response by reducing lesion areas and infiltrating myeloid cell numbers. We further revealed significantly decreased MCP1 levels in the spinal cord and serum after OECs transplantation ( P < 0.05). Noteworthily, distinct expression levels of MCP1 were found in rats undergoing a mild injury (cord impacted from a 10-mm height) compared to the moderate injury (25-mm) group. Our study reports that transplantation of OECs promotes locomotor functional recovery after SCI and alleviates acute inflammation by decreasing local and serological MCP1 levels. We provide preliminary evidence that MCP1 might serve as a potential biomarker to reflect the severity of SCI, which is of great interest in future studies.

Anti-Inflammatory Potential of Fucoidan for Atherosclerosis: In Silico and In Vitro Studies in THP-1 Cells

Several diseases, including atherosclerosis, are characterized by inflammation, which is initiated by leukocyte migration to the inflamed lesion. Hence, genes implicated in the early stages of inflammation are potential therapeutic targets to effectively reduce atherogenesis. Algal-derived polysaccharides are one of the most promising sources for pharmaceutical application, although their mechanism of action is still poorly understood. The present study uses a computational method to anticipate the effect of fucoidan and alginate on interactions with adhesion molecules and chemokine, followed by an assessment of the cytotoxicity of the best-predicted bioactive compound for human monocytic THP-1 macrophages by lactate dehydrogenase and crystal violet assay. Moreover, an in vitro pharmacodynamics evaluation was performed. Molecular docking results indicate that fucoidan has a greater affinity for L-and E-selectin, monocyte chemoattractant protein 1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1) as compared to alginate. Interestingly, there was no fucoidan cytotoxicity on THP-1 macrophages, even at 200 µg/mL for 24 h. The strong interaction between fucoidan and L-selectin in silico explained its ability to inhibit the THP-1 monocytes migration in vitro. MCP-1 and ICAM-1 expression levels in THP-1 macrophages treated with 50 µg/mL fucoidan for 24 h, followed by induction by IFN-γ, were shown to be significantly suppressed as eight- and four-fold changes, respectively, relative to cells treated only with IFN-γ. These results indicate that the electrostatic interaction of fucoidan improves its binding affinity to inflammatory markers in silico and reduces their expression in THP-1 cells in vitro, thus making fucoidan a good candidate to prevent inflammation.

Impinging Flow Induces Expression of Monocyte Chemoattractant Protein-1 in Endothelial Cells Through Activation of the c-Jun N-terminal Kinase/c-Jun/p38/c-Fos Pathway

Monocyte chemoattractant protein-1 (MCP-1) is an important regulator of the formation and development of intracranial aneurysms. This study explored the molecular mechanisms underlying the induction of MCP-1 and related inflammatory factors in human umbilical vein endothelial cells (HUVECs) under hemodynamic conditions. A modified T chamber was used to simulate fluid flow at the bifurcation of the artery and wall shear stress on HUVECs invitro. Changes in HUVECs were analyzed in response to impinging flow. And HUVECs without impinging flow were used as the control group. Protein expression levels of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38, activator protein-1, and MCP-1 were detected by Western blot, and the messenger RNA expression levels of MCP-1, interleukin (IL)-1β, and IL-6 were determined by quantitative reverse transcription polymerase chain reaction. Under impinging flow, the phosphorylation levels of ERK, JNK, and p38, as well as the protein levels of MCP-1, c-Jun, and c-Fos, increased. The messenger RNA expression of MCP-1, IL-1β, and IL-6 also increased in HUVECs. Pretreatment of the HUVECs with inhibitors of JNK and p38 significantly attenuated the increased expression of MCP-1, IL-1β, and IL-6, while ERK inhibitors had no obvious effect. Under impinging flow, MCP-1 and inflammatory factors are regulated through the JNK/c-Jun/p38/c-Fos pathway and participate in EC inflammation.

Maslinic Acid Attenuates Ischemia/Reperfusion-Induced Acute Kidney Injury by Suppressing Inflammation and Apoptosis Through Inhibiting NF-κB and MAPK Signaling Pathway.

Inflammation and apoptosis are the major contributors to the mechanisms of acute kidney injury (AKI) due to renal ischemia-reperfusion injury (IRI). Maslinic acid (MA), a pentacyclic triterpene acid mostly found in dietary plants, the current study was to demonstrate the renoprotective effect of MA on IRI-induced AKI, and to investigate the role of inflammation and apoptosis-related signaling pathways as a molecular mechanism. C57BL/6J mice were subjected to IRI for 72 h, and MA was daily administered by intraperitoneal injection during this period. In parallel, rat renal proximal tubule cells (NRK52E) were prophylactically treated with MA and then exposed to hydrogen peroxide (H2O2). MA treatment significantly inhibited the mRNA expression of interleukin (IL-1β), tumor necrosis factor-α (TGF-α), monocyte chemoattractant protein-1 (MCP-1), and intercellular adhesion molecule-1(ICAM-1). Also, MA reduced the expression of Bax/Bcl2 ratio and cleaved caspase-3. In NRK52 cells, MA inhibited the IκBα degradation, blocked NF-κB/p65 phosphorylation, and nuclear translocation. The phosphorylation of ERK, JNK, and p38 was attenuated by MA in IRI-induced kidney injury and H2O2-stimulated NRK52 cells. The expression levels of IL-1β, MCP-1, and ICAM-1 were upregulated in H2O2-stimulated NRK52E cells, which was attenuated by NF-κB inhibitor. H2O2 treatment increased the Bax/Bcl2 ratio and cleaved caspase-3 in NRK52E cells, which was counteracted by MAPK inhibitors. Together, our data demonstrate that MA suppresses IR-induced AKI injury through NF-κB and MAPK signaling pathways and that MA is a promising agent in the treatment of kidney diseases.

Microcystin-LR incorporated into colonic cells through probenecid-sensitive transporters leads to upregulated MCP-1 expression induced by JNK activation

Harmful algae that inhabit eutrophic lakes produce cyanotoxic microcystins. Therefore, the relationship between chronic exposure to microcystins via drinking water and organ disorders has been investigated. The present study aimed to determine whether representative microcystin-LR is involved in increased monocyte chemoattractant protein-1 (MCP-1) expression in rat colonic mucosa and enterocyte-like differentiated Caco-2 cells. The mRNA expression of MCP-1 was increased in the colons of rats administered with microcystin-LR, compared with controls. Furthermore, mRNA levels of MCP-1 expression significantly and positively correlated with those of Adhesion G Protein-Coupled Receptor E1 (ADGRE1; EMR1; F4/80), an indicator of macrophage infiltration, suggesting that increased MCP-1 expression induced by microcystin-LR promotes macrophage infiltration into the colon. Microcystin-LR increased MCP-1 expression in enterocyte-like differentiated Caco-2 cells, by activating c-Jun N-terminal kinase (JNK), but not extracellular signal-regulated kinase (ERK) or p38. The findings of transporter inhibitors indicated that microcystin-LR is incorporated into cells via ATP Binding Cassette (ABC) or solute carrier (SLC) transporters other than the organic anion transporting polypeptides (OATPs)1B1, 1B3, 2B1, and 1A2, which this leads to increased MCP-1 expression in the colon through activating JNK. Thus, increased MCP-1 expression induced by microcystin-LR might be a trigger for initiating tumorigenesis with inflammation in the colon because increased MCP-1 expression induces inflammation associated with macrophage infiltration into the colon, and chronic inflammation is associated with the initiation of tumorigenesis.

Expression levels of MCP-1, HGF, and IGF-1 in endometriotic patients compared with non-endometriotic controls

BackgroundTo study the concentrations of monocyte chemoattractant protein-1 (MCP-1), hepatocyte growth factor (HGF), and insulin-like growth factor-1 (IGF-1) in peritoneal fluid (PF) and serum, and to evaluate their expressions by PF and peripheral blood mononuclear cells (PFMCs and PBMCs, respectively), and ectopic and eutopic endometrial stromal cells of patients with endometriosis (EESCs and EuESCs, respectively) compared with controls.MethodsThe concentrations of mentioned cytokines in serum and PF, as well as their expression in PBMCs, PFMCs, EuESCs and EESCs from endometriosis patients and controls were assessed.ResultsThe levels of MCP-1, HGF, and IGF-1 in serum and PF in women with endometriosis were significantly higher than the controls (P < 0.05–P < 0.001). Gene expression of MCP-1 and IGF-1 in the PFMCs, PBMCs and EESCs also showed an increased level compared to controls (P < 0.05–P < 0.01). The protein expression of MCP-1 and IGF-1 by PFMCs was statistically higher in endometriotic women (P < 0.05 and P < 0.01, respectively). The gene and protein expression of HGF in PFMCs and its gene expression by EESCs were significantly higher in endometriotic women compared to controls (P < 0.05–P < 0.01).ConclusionsThe higher concentrations of mentioned cytokines in serum and PF and their higher expression by PFMCs and EESCs in endometriosis patients may contribute to the development of endometriosis.

Exploring the role of monocyte chemoattractant protein-1 in fibroblast-like synovial cells in rheumatoid arthritis

BackgroundRheumatoid arthritis (RA) is a chronic systemic inflammatory disease with persistent synovitis. In the present study, the impact of monocyte chemoattractant protein-1 (MCP-1) was explored to determine methods for the diagnosis and treatment of RA.MethodsFirst, fibroblast-like synoviocytes (FLSs) were obtained from a collagen-induced rat RA model. Next, MCP-1-overexpression plasmid and small interfering RNA were transfected into human and rat FLSs. Cell Counting Kit-8 (CCK-8), Transwell migration and flow cytometry assays were used to analyze cell proliferation, migration and apoptosis of FLSs following MCP-1 transfections, respectively. Furthermore, western blotting was used to analyze the expression levels of p-P38, p-PI3K, PI3K, CD31, VEGF, TNF-α and IL-β in FLSs following MCP-1 transfection. In addition, reverse transcription-quantitative PCR and ELISAs were used to analyze the expression levels of C-reactive protein (CRP), estrogen receptor, MCP-1 and pentraxin-3 in patients with clinical RA, followed by correlation analysis of clinical data. Finally, expression validation, diagnostic and protein-protein interaction (PPI) network analysis of MCP-1 were performed.ResultsMCP-1 promoted FLS proliferation and migration, and affected the apoptosis of FLSs. In addition, the expression levels of p-P38, p-PI3K, PI3K, CD31, VEGF, TNF-α and IL-β were also affected by MCP-1. In patients with clinical RA, the expression level of MCP-1 was increased. Moreover, CRP expression level was significantly up-regulated in RA. Clinically, MCP-1 was strongly correlated with tender joint count, swollen joint count, visual analog scale for general health and disease activity score 28 (DAS28)-MCP-1, and was moderately correlated with DAS28 and DAS28-CRP. PPI analysis showed that MCP-1 mainly interacted with other inflammatory cytokines.ConclusionIn conclusion, MCP-1 may play a significant regulatory role in RA, and could be used as a measurement index of clinical RA activity.

The Anti-inflammatory Protein TSG-6 Induced by S. aureus Regulates the Chemokine Function of Endothelial Cells In Vitro by Inhibiting the Chemokine-Glycosaminoglycan Interaction

The aim of this study was to explore the effect of the anti-inflammatory protein TSG-6 induced by Staphylococcus bacteria on the regulation of chemokine function in endothelial cells by inhibiting the chemokine-glycosaminoglycan interaction. To cultivate human umbilical vein endothelial cells and Staphylococcus aureus bacteria, respectively, after the experiment is divided into the control group, S. aureus bacteria-induced group, S. aureus bacteria glycosaminoglycans about 1 mg/L sugar group, S. aureus bacteria glycosaminoglycans about 5 mg/L sugar group, and S. aureus bacteria glycosaminoglycans about 10 mg/L sugar group, E-selectin; intercellular adhesion molecule-1 (ICAM-1); monocyte chemoattractant protein-1 (MCP-1); interleukin-8 (IL-8) expression level; chemokine CXCL9, CXCL10, and CXCL11 mRNA and protein expression level; and TSG mRNA and protein expression level were determined in each cell; the endothelial cell proliferation and vascular endothelial cell function indicators were analyzed. The expression levels of E-selectin, ICAM-1, IL-8, MCP-1, and chemokines CXCL9, CXCL10, and CXCL11 mRNA and protein in each group at 6, 12, and 24 h were significantly different (P < 0.05). TSG mRNA and protein expression levels, endothelial cell proliferation ability, and vascular endothelial cell function were also significantly different (P < 0.05). The expression levels of E-selectin, ICAM-1, IL-8, MCP-1, endothelial cell proliferation ability, and vascular endothelial cell function in the Staphylococcus aureus-induced group were lower than those in the control group and the Staphylococcus aureus glycosaminoglycan group, and the mRNA and protein expression levels of chemokines CXCL9, CXCL10, and CXCL11, and TSG mRNA and protein expression levels were higher. With the increase of glycosaminoglycan concentration, the above indexes were improved. The anti-inflammatory protein TSG-6 induced by S. aureus can regulate the chemokine function of endothelial cells by inhibiting the chemokine-glycosaminoglycan interaction.

Correlation between inflammatory cytokines and liver cancer stem cell markers in DEN-induced liver cancer rats.

To study the association of inflammatory factors and hepatocarcinoma stem cells of induced liver cancer rats. 30 SD male healthy rats were selected. 10 rats were given water as normal control group. 10 rats only were implemented laparotomy as sham operation group. The remaining 10 rats were the liver cancer model group and treated with diethylnitrosamine (DEN) to induce liver cancer. Real-time quantitative PCR was used to detect the related inflammatory factors in HCC tissues, including interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), transforming growth factor-β1 (TGF-β), human interleukin-1α (IL-1α), human interleukin 1β (IL-1β) and levels of hepatocarcinoma stem cells indicators CD90, CD133, Alpha-fetoprotein (AFP). Correlation analysis was used to analyze the correlation between inflammatory factors and hepatocarcinoma stem cells markers CD90 and CD133. The expression levels of IL-6, MCP-1 and TGF-β of HCC tissues in liver cancer model group were significantly higher than those in the control group and the sham operation group. The expression levels of CD90 and CD133 of tissues in the liver cancer model group were significantly higher than those in the control group and the sham operation group. The differences were statistically significant (p<0.001). By inhibiting related inflammatory factors, the growth, migration and invasion of liver cancer cells were significantly inhibited, and apoptosis was promoted. Correlation analysis results showed that the expression changes of IL-6, MCP-1 and TGF-β were significantly positively correlated with CD90 up-regulation (p<0.05), while the expression changes of IL-6, MCP-1 and TGF-β were significantly positively correlated with CD133 up-regulation (p<0.05). The inflammatory factors IL-6, MCP-1 and TGF-β are closely related to hepatocarcinoma stem cells, which play an important role in promoting the occurrence and deterioration of liver cancer.

Chlamydia psittaci Plasmid-Encoded CPSIT_P7 Elicits Inflammatory Response in Human Monocytes via TLR4/Mal/MyD88/NF-κB Signaling Pathway.

The chlamydial plasmid, an essential virulence factor, encodes plasmid proteins that play important roles in chlamydial infection and the corresponding immune response. However, the virulence factors and the molecular mechanisms of Chlamydia psittaci are not well understood. In the present study, we investigated the roles and mechanisms of the plasmid-encoded protein CPSIT_P7 of C. psittaci in regulating the inflammatory response in THP-1 cells (human monocytic leukemia cell line). Based on cytokine arrays, CPSIT_P7 induces the expression of interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1) in THP-1 cells. Moreover, the expression levels of IL-6, IL-8, and MCP-1 stimulated by CPSIT_P7 declined after silencing of the Toll-like receptor 4 (TLR4) gene using small interfering RNA and transfection of a dominant negative plasmid encoding TLR4 (pZERO-hTLR4). We further demonstrated that transfection with the dominant negative plasmid encoding MyD88 (pDeNy-hMyD88) and the dominant negative plasmid encoding Mal (pDeNy-hMal) could also abrogate the expression of the corresponding proteins. Western blot and immunofluorescence assay results showed that CPSIT_P7 could activate nuclear factor κB (NF-κB) signaling pathways in THP-1 cells. Altogether, our results indicate that the CPSIT_P7 induces the TLR4/Mal/MyD88/NF-κB signaling axis and therefore contributes to the inflammatory cytokine response.

Promising Effects of Zerumbone on the Regulation of Tumor-promoting Cytokines Induced by TNF-α-activated Fibroblasts.

Inflammation plays an important role in the development of several cancers. Inflammatory cytokines, including tumor necrosis factor-α (TNF-α), are associated with the induction of inflammation. Chronic inflammation contributes to the progression of cancer through several mechanisms, including increased cytokine production and activation of transcription factors, such as nuclear factor-κB (NF-κB). Zerumbone (ZER), a component of subtropical ginger (Zingiber zerumbet Smith), seems to have anti-inflammatory, anti-cancer, and antioxidant activities. In this study, we aimed to explore the protective function and mechanisms of ZER against TNF-α-induced cancer-promoting cytokines. We found that the viability of stimulated human fibroblast cell lines was reduced after treatment with ZER (IC50=18 µmol/L), compared to un-stimulated fibroblasts (IC50=40 µmol/L). Besides, ZER inhibited mRNA expression and protein secretion of transforming growth factor-β (TGF-β), interleukin-33 (IL-33), monocyte chemoattractant protein-1 (MCP-1), and stromal cell-derived factor 1 (SDF-1), which were produced by TNF-α-induced fibroblasts, as measured by quantitative real time-PCR (qRT-PCR) and ELISA assays. The mRNA expression levels of TGF-β, IL-33, SDF-1, and MCP-1 showed 8, 5, 2.5, and 4-fold reductions, respectively. Moreover, secretion of TGF-β, IL-33, SDF-1, and MCP-1 was reduced to 3.65±0.34 ng/mL, 6.3±0.26, 1703.6±295.2, and 5.02±0.18 pg/mL, respectively, compared to the untreated group. In addition, the conditioned media (CM) of TNF-α-stimulated fibroblasts increased the NF-κB expression in colorectal cancer cell lines (HCT-116 and Sw48), while in the vicinity of ZER, the expression of NF-κB was reversed. Considering the significant effects of ZER, this component can be used as an appropriate alternative herbal treatment for cancer-related chronic inflammation.

Monocyte Chemoattractant Protein-1 promotes cancer cell migration via c-Raf/MAPK/AP-1 pathway and MMP-9 production in osteosarcoma

BackgroundOsteosarcoma is generally reported among younger individuals and has a very poor prognosis, particularly for the development of metastasis. However, more effective metastatic biomarkers and therapeutic methods are absent. Monocyte chemoattractant protein-1 (MCP-1) is involved in cancer progression and inflammatory recruitment. Although previous studies have reported higher serum MCP-1 levels in patients with osteosarcoma, the role of MCP-1 in osteosarcoma progression remains to be addressed.MethodsThe osteosarcoma cell migratory ability was assessed by transwell migration assay. The MCP-1 and MMP-9 expression levels were analyzed by Western blot and qPCR. The signal activation was conducted by Western blot. The in vivo mouse experiment and tumor tissue array were performed to confirm our findings in vitro.ResultsThe present study demonstrates that MCP-1 regulates cell mobility through matrix metalloproteinase (MMP)-9 expression in osteosarcoma cells. Moreover, MCP-1 promotes MMP-9 expression, cell migration, and cell invasion by mediating CCR2, c-Raf, MAPK, and AP-1 signal transduction. Using MCP-1 knockdown stable cell lines, we found that MCP-1 knockdown reduces MMP-9 expression and cell mobility. Finally, we found high MCP-1 expression levels in osteosarcoma specimens.ConclusionsOur results provide prognostic value of MCP-1 in osteosarcoma by promoting MMP-9 expression.

Protective Effect of S-Allyl Cysteine Against Neonatal Asthmatic Rats.

S-Allyl cysteine (SAC), an organic compound and a natural constituent of Allium sativum, commonly known as garlic have been consumed in routine foods are known to possess various biological activities. Nevertheless, scientific evidence on the protective effect of SAC against neonatal asthmatic rats is not available. Hence, the present study aimed at investigating the anti-asthmatic activity of SAC in neonatal asthmatic rats using Wistar rats. The study conducted in 4 groups consists of normal control rats, asthma-induced, asthma animals administered with SAC (25 mg/kg), and SAC control. At the end of the experimental period, inflammatory cells in bronchoalveolar lavage fluid (BALF), inflammatory markers, fibrinogen level, activated partial thromboplastin time, coagulation factor activity, and histopathology were elucidated. The current investigation exhibits that SAC significantly reduced the total leukocytes, with restored fibrinogen level, and activated partial thromboplastin time. In addition, the levels of inflammatory cytokines such as TNF-α (tumor necrosis factor- α), IL-6 (Interleukin 6), and IL-1β have also attenuated in SAC treated animals. Furthermore, the mRNA expression levels of COX2 (cyclooxygenase-2), MCP-1 (monocyte chemoattractant protein-1), RANTES (regulated upon activation, normal T cell expressed and secreted), and eotaxin were reduced in SAC treated animals. Treatment of rats with SAC significantly reduced inflammation and eosinophil infiltration in the lungs. These results suggest that SAC exert protection in neonatal asthmatic rats suffering from acute or chronic inflammation by inducing anti-inflammatory and cell-protective responses.

The high expression of the pain-related inflammatory factors in the eyes of cataract patients infected with hepatitis B virus

In cataract surgery, it is often found that patients infected hepatitis B virus (HBV) are likely to suffer from more pain than other patients. In order to assess the inflammation status of the aqueous humor in the eyes of cataract patients infected with HBV. RayBio Human Inflammation Array was used to assay aqueous humor samples collected from 14 eyes of patients infected with HBV and 14 eyes of cataract patients without HBV infection (the controls) during the cataract surgery. RayBio Human Quantibody Cutom Array was adopted for the validation of the screened cytokines, with aqueous humor samples collected from 40 eyes of patients infected with HBV and 40 eyes of the controls. A pain questionnaire survey about the surgery was conducted in all patients after operation. The results of questionnaire showed that patients infected with HBV were more likely to have pain during operation. The Human Inflammation Array revealed that the expression levels of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor α (TNF-α) and tumor necrosis factor β (TNF-β) were very high in HBV infected patients and IL-1ra was much lower in patients infected with HBV (all, P < 0.05). In validation, the Human Quantibody Cutom Array revealed that the expression levels of MCP-1 and TNF-α were high in HBV infected patients with significant difference (all P < 0.05). These results revealed that pain-related inflammatory factors MCP-1 and TNF-α were increased in aqueous humor of cataract patients infected with HBV, which indicates that patients infected with HBV may be more prone to intraoperative pain.