There is growing evidence that interleukin(IL)-6 plays an important role in neurological and psychiatric disorders.This editorial comments on the study published in the recent issue of the World Journal of Psychiatry,...There is growing evidence that interleukin(IL)-6 plays an important role in neurological and psychiatric disorders.This editorial comments on the study published in the recent issue of the World Journal of Psychiatry,which employed Mendelian randomization to identify a causal relationship between IL-6 receptor blockade and decreased epilepsy incidence.The purpose of this editorial is to highlight the dual effects of IL-6 in epilepsy and its related neuropsychiatric comorbidities.IL-6 plays a critical role in the facilitation of epileptogenesis and maintenance of epileptic seizures and is implicated in neuroinflammatory proce-sses associated with epilepsy.Furthermore,IL-6 significantly influences mood regulation and cognitive dysfunction in patients with epilepsy,highlighting its involvement in neuropsychiatric comorbidities.In summary,IL-6 is not only a pivotal factor in the pathogenesis of epilepsy but also significantly contributes to the emergence of epilepsy-related neuropsychiatric complications.Future resear-ch should prioritize elucidating the specific mechanisms by which IL-6 operates across different subtypes,stages and neuropsychiatric comorbidities of epilepsy,with the aim of developing more precise and effective interventions.Furthermore,the potential of IL-6 as a biomarker for the early diagnosis and prognosis of epile-psy warrants further investigation.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal prognosis.Immunotherapy has become an important treatment strategy for HCC,as immunity is closely related to inflammation in th...BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal prognosis.Immunotherapy has become an important treatment strategy for HCC,as immunity is closely related to inflammation in the tumor microenvir-onment.Inflammation regulates the expression of programmed death ligand-1(PD-L1)in the immunosuppressive tumor microenvironment and affects im-munotherapy efficacy.Interleukin-17A(IL-17A)is involved in the remodeling of the tumor microenvironment and plays a protumor or antitumor role in different tumors.We hypothesized that IL-17A participates in tumor progression by affe-cting the level of immune checkpoint molecules in HCC.The upregulation of PD-L1 expression in HCC cells by IL-17A was assessed by reverse transcription PCR,western blotting,and flow cytometry.Mechanistic studies were conducted with gene knockout models and pathway inhibitors.The function of IL-17A in immune evasion was explored through coculture of T cells and HCC cells.The effects of IL-17A on the malignant biological behaviors of HCC cells were evaluated in vitro,and the antitumor effects of an IL-17A inhibitor and its synergistic effects with a PD-L1 inhibitor were studied in vivo.RESULTS IL-17A upregulated PD-L1 expression in HCC cells in a dose-dependent manner,whereas IL-17A receptor knockout or treatment with a small mothers against decapentaplegic 2 inhibitor diminished the PD-L1 expression induced by IL-17A.IL-17A enhanced the survival of HCC cells in the coculture system.IL-17A increased the viability,G2/M ratio,and migration of HCC cells and decreased the apoptotic index.Cyclin D1,VEGF,MMP9,and Bcl-1 expression increased after IL-17A treatment,whereas BAX expression decreased.The combination of IL-17A and PD-L1 inhibitors showed synergistic antitumor efficacy and increased cluster of differentiation 8+T lymphocyte infiltration in an HCC mouse model.CONCLUSION IL-17A upregulates PD-L1 expression via the IL-17A receptor/phosphorylation-small mothers against decapenta-plegic 2 signaling pathway in HCC cells.Blocking IL-17A enhances the therapeutic efficacy of PD-L1 antibodies in HCC in vivo.展开更多
Sepsis is a life-threatening condition caused by a dysregulated response of the body in response to an infection that harms its tissues and organs.Interleukin-6(IL-6)is a significant component of the inflammatory resp...Sepsis is a life-threatening condition caused by a dysregulated response of the body in response to an infection that harms its tissues and organs.Interleukin-6(IL-6)is a significant component of the inflammatory response as part of the pa-thogenesis of sepsis.It aids in the development of Acute lung injury and,subse-quently,multiple organ dysfunction syndrome.This letter probes into the corre-lation between plasma IL-6 levels and the risk of developing acute lung injury and multiple organ dysfunction syndrome in critically ill patients with sepsis.While it shows promising results,limitations like its observational study design,a limited sample size,a single center involvement,single-time-point measurement,and a lack of a control group restrain its cogency.The study is a big step in identifying IL-6 as a biomarker to improve patient care.展开更多
AIM:To evaluate the proinflammatory effects and molecular mechanisms of interleukin(IL)-17 in intestinal epithelial cell line HT-29.METHODS:HT-29 cells were cultured with IL-17,tumor necrosis factor(TNF)-α,or the com...AIM:To evaluate the proinflammatory effects and molecular mechanisms of interleukin(IL)-17 in intestinal epithelial cell line HT-29.METHODS:HT-29 cells were cultured with IL-17,tumor necrosis factor(TNF)-α,or the combination of both IL-17 and TNF-α.Real-time PCR and Western blot were used to measure the gene expression levels of neutrophil chemokines CXCL1,CXCL2,CXCL5,CXCL6,IL-8and TH-17 cell chemokine CCL20,the phosphorylation levels of p38 and TNF-α,and the expression level of IL-8,after using the p38 inhibitor in HT-29 cells.The stable Act1 knockdown HT-29 cell line was established to further test the phosphorylation changes of p38,after using IL-17 and TNF-α.RESULTS:After HT-29 cells were cultured with IL-17and TNF-α,the expression levels of neutrophil chemokines(CXCL1,CXCL2,CXCL5,CXCL6,IL-8)and Th17chemokine(CCL20)significantly improved(24.96±2.53,28.47±2.87,38.08±2.72,33.47±2.41,31.7±2.38,44.37±2.73,respectively),and the differences were all statistically significant(P<0.01).Western blot results showed that IL-17 obviously enhanced the phosphorylation level of p38,which was induced by TNF-α.Compared with the control group,the expression level of IL-8 significantly declined(9.47±1.36 vs 3.06±0.67,P<0.01)when TH-29 cells were cultured with IL-17and TNF-α.p38 inhibition assay showed that the p38pathway played an essential role in the inflammatory response induced by IL-17.p38 phosphorylation levels could not be changed after using IL-17 and TNF-αin the stable Act1 knockdown HT-29 cell line.CONCLUSION:IL-17 significantly promoted the gene expression levels of TNF-α-induced neutrophil chemokines and Th17 cell chemokine.It is obvious that IL-17and TNF-αhave synergistic effects on p38.展开更多
AIM:To study the effect of probiotics on interleukin-8 secretion in intestinal epithelia when stimulated by proinflammatory cytokines.METHODS: Colonic adenocarcinoma HT29 cells were cultured and divided into four grou...AIM:To study the effect of probiotics on interleukin-8 secretion in intestinal epithelia when stimulated by proinflammatory cytokines.METHODS: Colonic adenocarcinoma HT29 cells were cultured and divided into four groups:control,TNF-α (group T in short),bifidobacterium (group B), lactobacillus (group L). B. Longum and L. bulgaricus were suspended in culture medium with a concentration of 1×10^8cfu/ml and added into 24 wells respectively. One hour later TNF-α (10ng/ml) was added into each well of groups T, B, L. The supernatants were collected and measured for IL-8 after 3 hours, nuclear factor-κB (NF-κB) p65 was also examined by Western blotting.RESULTS:There was less interleukin-8 secretion in HT29 cells when preincubated with B. Longum or L. bulgaricus compared with group T.Less p65 appeared in nuclei in groups B and L compared with group T,as detected by Westem blot.CONCLUSION:Probiotics can suppress interleukin-8 secretion in intestinal epithelia when stimulated by proinflammatory cytokines, which is most likely mediated by NF-κB.展开更多
文摘There is growing evidence that interleukin(IL)-6 plays an important role in neurological and psychiatric disorders.This editorial comments on the study published in the recent issue of the World Journal of Psychiatry,which employed Mendelian randomization to identify a causal relationship between IL-6 receptor blockade and decreased epilepsy incidence.The purpose of this editorial is to highlight the dual effects of IL-6 in epilepsy and its related neuropsychiatric comorbidities.IL-6 plays a critical role in the facilitation of epileptogenesis and maintenance of epileptic seizures and is implicated in neuroinflammatory proce-sses associated with epilepsy.Furthermore,IL-6 significantly influences mood regulation and cognitive dysfunction in patients with epilepsy,highlighting its involvement in neuropsychiatric comorbidities.In summary,IL-6 is not only a pivotal factor in the pathogenesis of epilepsy but also significantly contributes to the emergence of epilepsy-related neuropsychiatric complications.Future resear-ch should prioritize elucidating the specific mechanisms by which IL-6 operates across different subtypes,stages and neuropsychiatric comorbidities of epilepsy,with the aim of developing more precise and effective interventions.Furthermore,the potential of IL-6 as a biomarker for the early diagnosis and prognosis of epile-psy warrants further investigation.
基金Supported by the Natural Science Foundation of Gansu Province,No.21JR7RA373 and No.24JRRA295.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal prognosis.Immunotherapy has become an important treatment strategy for HCC,as immunity is closely related to inflammation in the tumor microenvir-onment.Inflammation regulates the expression of programmed death ligand-1(PD-L1)in the immunosuppressive tumor microenvironment and affects im-munotherapy efficacy.Interleukin-17A(IL-17A)is involved in the remodeling of the tumor microenvironment and plays a protumor or antitumor role in different tumors.We hypothesized that IL-17A participates in tumor progression by affe-cting the level of immune checkpoint molecules in HCC.The upregulation of PD-L1 expression in HCC cells by IL-17A was assessed by reverse transcription PCR,western blotting,and flow cytometry.Mechanistic studies were conducted with gene knockout models and pathway inhibitors.The function of IL-17A in immune evasion was explored through coculture of T cells and HCC cells.The effects of IL-17A on the malignant biological behaviors of HCC cells were evaluated in vitro,and the antitumor effects of an IL-17A inhibitor and its synergistic effects with a PD-L1 inhibitor were studied in vivo.RESULTS IL-17A upregulated PD-L1 expression in HCC cells in a dose-dependent manner,whereas IL-17A receptor knockout or treatment with a small mothers against decapentaplegic 2 inhibitor diminished the PD-L1 expression induced by IL-17A.IL-17A enhanced the survival of HCC cells in the coculture system.IL-17A increased the viability,G2/M ratio,and migration of HCC cells and decreased the apoptotic index.Cyclin D1,VEGF,MMP9,and Bcl-1 expression increased after IL-17A treatment,whereas BAX expression decreased.The combination of IL-17A and PD-L1 inhibitors showed synergistic antitumor efficacy and increased cluster of differentiation 8+T lymphocyte infiltration in an HCC mouse model.CONCLUSION IL-17A upregulates PD-L1 expression via the IL-17A receptor/phosphorylation-small mothers against decapenta-plegic 2 signaling pathway in HCC cells.Blocking IL-17A enhances the therapeutic efficacy of PD-L1 antibodies in HCC in vivo.
文摘Sepsis is a life-threatening condition caused by a dysregulated response of the body in response to an infection that harms its tissues and organs.Interleukin-6(IL-6)is a significant component of the inflammatory response as part of the pa-thogenesis of sepsis.It aids in the development of Acute lung injury and,subse-quently,multiple organ dysfunction syndrome.This letter probes into the corre-lation between plasma IL-6 levels and the risk of developing acute lung injury and multiple organ dysfunction syndrome in critically ill patients with sepsis.While it shows promising results,limitations like its observational study design,a limited sample size,a single center involvement,single-time-point measurement,and a lack of a control group restrain its cogency.The study is a big step in identifying IL-6 as a biomarker to improve patient care.
基金Supported by Minhang District Natural Science Foundation(to Wang YL)the Science and Technology Commission in Shanghai,No.10411968500 National Natural Science Foundation of China,No.81001324
文摘AIM:To evaluate the proinflammatory effects and molecular mechanisms of interleukin(IL)-17 in intestinal epithelial cell line HT-29.METHODS:HT-29 cells were cultured with IL-17,tumor necrosis factor(TNF)-α,or the combination of both IL-17 and TNF-α.Real-time PCR and Western blot were used to measure the gene expression levels of neutrophil chemokines CXCL1,CXCL2,CXCL5,CXCL6,IL-8and TH-17 cell chemokine CCL20,the phosphorylation levels of p38 and TNF-α,and the expression level of IL-8,after using the p38 inhibitor in HT-29 cells.The stable Act1 knockdown HT-29 cell line was established to further test the phosphorylation changes of p38,after using IL-17 and TNF-α.RESULTS:After HT-29 cells were cultured with IL-17and TNF-α,the expression levels of neutrophil chemokines(CXCL1,CXCL2,CXCL5,CXCL6,IL-8)and Th17chemokine(CCL20)significantly improved(24.96±2.53,28.47±2.87,38.08±2.72,33.47±2.41,31.7±2.38,44.37±2.73,respectively),and the differences were all statistically significant(P<0.01).Western blot results showed that IL-17 obviously enhanced the phosphorylation level of p38,which was induced by TNF-α.Compared with the control group,the expression level of IL-8 significantly declined(9.47±1.36 vs 3.06±0.67,P<0.01)when TH-29 cells were cultured with IL-17and TNF-α.p38 inhibition assay showed that the p38pathway played an essential role in the inflammatory response induced by IL-17.p38 phosphorylation levels could not be changed after using IL-17 and TNF-αin the stable Act1 knockdown HT-29 cell line.CONCLUSION:IL-17 significantly promoted the gene expression levels of TNF-α-induced neutrophil chemokines and Th17 cell chemokine.It is obvious that IL-17and TNF-αhave synergistic effects on p38.
文摘AIM:To study the effect of probiotics on interleukin-8 secretion in intestinal epithelia when stimulated by proinflammatory cytokines.METHODS: Colonic adenocarcinoma HT29 cells were cultured and divided into four groups:control,TNF-α (group T in short),bifidobacterium (group B), lactobacillus (group L). B. Longum and L. bulgaricus were suspended in culture medium with a concentration of 1×10^8cfu/ml and added into 24 wells respectively. One hour later TNF-α (10ng/ml) was added into each well of groups T, B, L. The supernatants were collected and measured for IL-8 after 3 hours, nuclear factor-κB (NF-κB) p65 was also examined by Western blotting.RESULTS:There was less interleukin-8 secretion in HT29 cells when preincubated with B. Longum or L. bulgaricus compared with group T.Less p65 appeared in nuclei in groups B and L compared with group T,as detected by Westem blot.CONCLUSION:Probiotics can suppress interleukin-8 secretion in intestinal epithelia when stimulated by proinflammatory cytokines, which is most likely mediated by NF-κB.
