A new independent subtype CD4+ T cell which massively secreted interleukin-17 (IL-17) was found at the beginning of the 21st century, and thus it was named as T helper cell 17 (Th17 cell). With the progress of the research in recent years, Th17 cells were found to be widely involved in a variety of the human diseases such as autoimmune diseases, infections and tumors through secretion of IL-17. The relationship between Th17 cells, IL-17 and the occurrence, development and prognosis of lung cancer was reviewed.
ObjectiveTo explore the effects of simvastatin on the expression of matrix metalloproteinase (MMP) and inflammatory factors in rats with smoke-induced chronic obstructive pulmonary disease (COPD). Methods40 male Wistar rats were randomly divided into four groups, including a normal group (group A), a simvastatin group (group B), a COPD model group (group C) and a simvastatin intervention group (group D). The COPD model of the group C and D were induced through exposing to the cigarette smoke repeatedly. At the same time, the rats of group B and D were given by gavage 5 mg/(kg·d) with simvastatin, and the other two groups were given with the same volume saline for 16 weeks. Pulmonary function tests and pathological examination of the lung tissue were performed after the induction of COPD model. Enzyme-linked immunosorbent assay (ELISA) method was used to measure the content of MMP-2, MMP-9, IL-6, IL-8, TNF-α in lung tissue homogenate. ResultsThe airway resistance of group C and group D was significantly higher than the group A and group B (P<0.01), and the airway resistance of group D was significantly lower than group C (P<0.01). The degree of bronchial inflammation and emphysema of group C was more apparent than group D in the pathological section, and there were no bronchial inflammation and emphysema in group A and group B. The ELISA results showed that the contents of MMP-2, MMP-9, IL-6, IL-8, TNF-α in group C were all significantly higher than those in group D. ConclusionSimvastatin has inhibitory effect on pulmonary inflammation of COPD, and can reduce the expression of matrix metalloproteinase and inflammatory factors in the lung.
Objective To observe the changes of soluble triggering receptor expressed on myeloid cell-1 ( sTREM-1) and inflammatory mediators levels in plasma of severe pneumonia patients, and explore the significance of systemic inflammatory response state.Methods Plasma levels of sTREM-1, tumor necrosis factor-α ( TNF-α) and interleukin-10 ( IL-10) were examined in 40 patients with severe pneumonia, 25 patients with uncomplicated pneumonia, and 15 healthy volunteers. Plasma levels of TNF-α,IL-10 and sTREM-1 in survival and non-survival severe pneumoniawere observed on days 1,4, 7 and the day of discharge or death.Results Plasma levels of TNF-α, IL-10, and sTREM-1 [ ( 44. 25 ±10. 81) pg/mL,( 58. 21 ±16. 41) pg/mL, ( 51. 75 ±18. 51) pg/mL, respectively] in the patients with severe pneumonia were higher than those with uncomplicated pneumonia [ ( 24.6 ±6. 45) pg/mL, ( 24. 56 ±7. 1) pg/mL,( 25. 55 ±7. 72) pg/mL, respectively] and the normal controls [ ( 13. 82 ±4. 04) pg/mL, ( 15. 30 ±4. 45)pg/mL, ( 14. 37 ±4. 82) pg/mL, respectively] ( P lt;0. 001) . Plasma levels of TNF-α, IL-10, and sTREM-1 were gradually decreased in the survivors, while maintained at high levels or increased in the non-survivors.The levels of these mediators were all significantly higher in the non-survivors than the survivors at all time points. The ratio of TNF-α/ IL-10 level was higher in the severe pneumonia patients than the uncomplicated pneumonia patients and the control subjects ( 1. 286 ±0. 177 vs. 1. 077 ±0. 410 and 0. 932 ±0. 154) on day 1.The ratio of TNF-α/IL-10 level was higher in the non-survivors than the survivors at all time points. There was negative correlation between plasma levels of sTREM-1 and TNF-αon day 1 ( r = - 0. 479, P =0. 002) ,and positive correlation between plasma levels of sTREM-1 and IL-10 on day 1 ( r = 0. 326, P = 0. 040) .Conclusions There are excessive release of inflammatory mediators and unbalanced systemic inflammatory response in patients with severe pneumonia, especially in non-survivors. sTREM-1, TNF-α and IL-10 are involved in the inflammatory response, and their levels may reflect the prognosis.
ObjectiveTo systematically review the data of peripheral inflammatory markers in patients with Alzheimer’s disease (AD) and vascular dementia (VaD) to further indicate pathogenesis and antidiastole.MethodsPubMed, EMbase, The Cochrane Library, CNKI, WanFang Data and VIP databases were electronically searched to collect studies on peripheral inflammatory markers in patients with AD and VaD from inception to July 2020. Two reviewers independently screened literature, extracted data, and assessed risk of bias of included studies, and meta-analysis was performed by using Stata 15.1SE software.ResultsA total of 30 studies involving 2 377 patients were included. The results of meta-analysis showed that the IL-6 level was higher in VaD group than that in AD group (SMD=−0.477, 95%CI −0.944 to −0.009, P=0.046). However, there were no statistical difference in peripheral IL-1β (SMD=−0.034, 95%CI −0.325 to 0.257, P=0.818), TNF-α (SMD=0.409, 95%CI −0.152 to 0.970, P=0.153) or CRP (SMD=0.277, 95%CI −0.228 to 0.782, P=0.282) levels.ConclusionsThese findings suggest that IL-6 may be sensitive markers to distinguish AD from VaD. Due to limited quality and quantity of the included studies, more high-quality studies are required to verify the conclusions.
ObjectiveTo analyze the correlations between the immune function and inflammatory factors levels of patients with hepatocellular carcinoma (HCC) and the results of in vitro high-throughput drug sensitivity, and to provide a reference for personalized drug selection for patients with HCC. MethodsThe patients with HCC who met the inclusion criteria from December 2019 to June 2021 in the First Affiliated Hospital of Chongqing Medical University were included. The HCC cells were used to perform in vitro high-throughput drug sensitivity screening, the result was classified into sensitive and insensitive. The correlations between drug sensitivity results and immune function and inflammatory factors levels of corresponding patients were analyzed, and the relation between these indexes (P<0.05) and drug sensitivity of HCC cells to drugs or combination regimen of drugs was further analyzed by univariate logistic regression. ResultsA total of 74 patients with HCC were included in this study. The results showed that the level of interleukin-6 was negatively correlated with sorafenib, caffezomib, gemcitabine, oxaliplatin + epirubicin + irinotecan + 5-fluorouracil, oxaliplatin + irinotecan + epirubicin, and oxaliplatin + epirubicin regimens on the inhibition rates of HCC in vitro (P<0.05), and positively correlated with bortezomib (P<0.05). However, the level of interleukin-6 was not related to the sensitivity of HCC cells to these single drugs or combined regimens (P>0.05). Meanwhile it was found that tumor necrosis factor (TNF)-α was negatively correlated with cabotinib, apatinib, caffezomib, and epirubicin on the inhibition rates of HCC in vitro (P<0.05), and positively correlated with epirubicin (P<0.05). But only it was found that tumor necrosis factor-α level was related to the sensitivity of HCC cells to epirubicin (P<0.05). ConclusionsTumor necrosis factor-α level in peripheral blood of patients with HCC has a certain relation with epirubicin on inhibition rate of HCC in vitro and it might have a certain value in predicting sensitivity of HCC cells to epirubicin. Meanwhile, although it is found that level of IL-6 is related to sorafenib, caffezomib, gemcitabine, or including combination regiems including oxaliplatin and epirubicin on inhibition rates of HCC in vitro, their value is not found in predicting sensitivity of HCC cells to these single drugs or combined regimens.
Objective To investigate the regulatory effects of SHP2 inhibition on the secretion of macrophage-associated inflammatory factors in KRAS-mutant lung cancer cells and to elucidate the underlying mechanisms by which this inhibition remodels the tumor immune microenvironment. Methods Three KRAS-mutant lung cancer cell lines were treated with the SHP2 inhibitor SHP099. The levels of phosphorylated SHP2 and ERK were assessed by Western blot. The expression levels of related inflammatory factors were analyzed using Luminex assay and qRT-PCR assay. Transcriptome sequencing was performed to identify differentially expressed genes and conduct KEGG pathway enrichment analysis. The expression of CXCL8 was validated by flow cytometry and Western blot. Survival analysis and gene set correlation analysis were conducted based on the TCGA database. Results SHP099 significantly inhibited the expression of p-SHP2 and p-ERK proteins, and reduced the secretion of multiple macrophage-related inflammatory factors. qRT-PCR confirmed a decrease in CXCL8 mRNA levels. Transcriptome analysis revealed significant enrichment of the rheumatoid arthritis pathway. Flow cytometry and Western blot validated a significant reduction in CXCL8 protein expression. Survival analysis showed that patients with KRAS-mutant lung adenocarcinoma and high CXCL8 expression had a shorter overall survival, and CXCL8 was positively correlated with M2 macrophage marker genes. Conclusion Targeted inhibition of SHP2 can suppress the expression of some macrophage-related inflammatory factors in KRAS-mutant lung cancer cells, with the most significant inhibition of CXCL8 expression. The mechanism may involve SHP2 regulating the transcription factor AP-1.
Objective To investigate the influence of proteasome inhibitorMG-132 on inflammatory factors in COPD rats and its potential mechanism. Methods The COPD rat model was established by instillation of lipopolysaccharide and exposure to cigarette smoke. Then the rats were randomly divided into 4 groups( n = 12 in each group) , ie. a COPD model group, a COPD + MG-132 low concentration group ( 0. 05 mg·kg- 1·d - 1 ) , a COPD + MG-132 high concentration group( 0. 1 mg· kg- 1 · d - 1 ) , and a normal control group. The rats were injected intraperitoneally with different dose of MG-132 or normal saline. After 1 week and 4 weeks, 6 rats in each group were sarcrificed. Then the following parameters were determined including histopathological changes of lung tissue, and the concentrations of IL-1β, IL-6, IL-8 in serum and diaphragm via ELISA. Results The lung histopathological examination showed obvious emphysema and inflammatory infiltration in the COPD rats. These pathological changes were obviously ameliorated in two MG-132 treatment groups. The IL-1β, IL-6, and IL-8 levels in serumand diaphragmin the COPD model group were all significantly increased from1 week and 4 week than those in the normal control group( P lt;0. 05) .MG-132 down-regulated the expression of these inflammatory factors in a time-and dosedependent manner. The IL-1β, IL-6, and IL-8 levels in serum and diaphragm in the MG-132 low concentration group and high concentration group were all decreased compared with the COPD model group ( P lt; 0. 05) . Conclusion COPD is a systemic inflammatory disease which can be inhibited by the proteasome inhibitor MG-132 through suppressing inflammatory factors.
ObjectiveThis study applied Mendelian randomization to explore the potential causal relationship between inflammatory factors and diabetic nephropathy. MethodsSummary-level data from genome-wide association studies of inflammatory factors and diabetic nephropathy were used, and inverse variance weighted analysis was used as the primary analytical method, complemented by results from weighted median, MR-Egger regression, simple model, and median model approaches. Sensitivity analysis was used to test the reliability of the MR analysis results. ResultsIn the inverse variance weighted method, stem cell factor (OR=1.28, 95%CI 1.04 to 1.58, P=0.020) and interferon-γ (OR=1.36, 95%CI 1.10 to 1.70, P=0.005) were positively correlated with diabetic nephropathy, and diabetic nephropathy was positively correlated with interferon-inducible protein 10 (OR=0.90, 95%CI 0.83 to 0.98, P=0.012) were negatively correlated with diabetic nephropathy. Sensitivity analysis showed that MR analysis was reliable. ConclusionStem cell factors and interferon-γ are associated with an increased risk of developing diabetic nephropathy, and diabetic nephropathy decreases the expression of interferon-inducible protein 10 in vivo. Our results demonstrate a potential causal relationship between inflammatory factors and the development of diabetic nephropathy. This finding is of clinical significance for the pre-diagnosis and treatment of diabetic nephropathy.