Background: Interleukin-37 b(IL-37 b), a vital negative regulator of the innate immune system, has been reported to be a tumor inhibitor in different type of cancers. However, little is known about the relationship be...Background: Interleukin-37 b(IL-37 b), a vital negative regulator of the innate immune system, has been reported to be a tumor inhibitor in different type of cancers. However, little is known about the relationship between IL-37 b and hepatocellular carcinoma(HCC). The present study aimed to investigate the potential roles of IL-37 b in HCC progression. Methods: Subjects( n = 237) were recruited, and serum IL-37 b was measured using ELISA. The tumorsuppressive capacity and underlying mechanisms of IL-37 b in HCC were investigated in vitro and in vivo. Results: Compared to healthy controls, serum IL-37 b levels were elevated in chronic hepatitis B(CHB) patients but decreased significantly in HBV-HCC patients, especially for those with portal venous tumor thrombus. Low level serum IL-37 b in HBV-HCC patients correlated with high HCC stage and poor overall survival and disease-free survival. In vitro and in vivo, recombinant human IL-37 b inhibited proliferation and metastasis in HCC cells. Furthermore, IL-37 b inhibited epithelial mesenchymal transition in HCC cells in vitro by downregulating IL-6, pSTAT3(Y705), N-cadherin, and vimentin expression and by upregulating E-cadherin expression. These effects were partially reversed by transfection of adenovirus encoding human IL-6. Conclusions: IL-37 b inhibits HCC growth, metastasis and epithelial mesenchymal transition by regulating IL-6/STAT3 signaling. Serum IL-37 b may be a biomarker for HBV-HCC and its staging.展开更多
Objective: To explore the effect of miR-223 on the expression of inflammatory factors and renal interstitial fibrosis in a rat model of chronic glomerulonephritis based on the interleukin 6/signal transducer and activ...Objective: To explore the effect of miR-223 on the expression of inflammatory factors and renal interstitial fibrosis in a rat model of chronic glomerulonephritis based on the interleukin 6/signal transducer and activator of transcription 3(IL-6/STAT3) signaling pathway. Methods: A total of 70 SPF-grade healthy adult male SD rats were selected, and were randomly divided into five groups. Except for the blank group, the remaining four groups of rats were all subcutaneously injected with 1 mg/m L cationized bovine serum albumin(C-BSA) emulsion at multiple points(in the first week) and injected with 2.5 mg/m L C-BSA solution through the tail vein(from the 2nd to 4th week) to establish a glomerulonephritis model. After successful modeling, the blank group and the modeling group were injected with normal saline through the tail vein, the negative control group was injected with 50 μg/kg NC agomir through the tail vein, the miR-223 agonist group was injected with 50 μg/kg miR-223 agomir through the tail vein, and the pathway activation group was injected with 50 μg/kg miR-223agomir and 1 μg/kg rh IL-6 through the tail vein. After continuous treatment for 21 d,the rats were sacrificed and kidney tissues were taken. The expression of miR-223, inflammatory factors and IL-6/STAT3 signaling pathway-related proteins in the five groups of rats was observed and compared, and the renal interstitial fibrosis in the five groups of rats was also observed and compared. Results: The relative expression level of miR-223 in the blank group was significantly higher than that in the other four groups. The relative expression levels of miR-223 in the miR-223 agonist group and the pathway activation group were significantly higher than those in the model group and the negative control group(P<0.05). The expression levels of IL-1β, IL-17, TNF-α, and TGF-β1 in the blank group were lower than those in the other four groups. The expression levels of IL-1β, IL-17, TNF-α, and TGF-β1 in the model group and the negative control group were significantly higher than those in the miR-223 agonist group and the pathway activation group. The expression levels of IL-1β, IL-17, TNF-α,and TGF-β1 in the pathway activation group were higher than those in the miR-223agonist group(P<0.05). The proportion of renal interstitial fibrosis area in renal tissue of the blank group was significantly lower than that in the other four groups. The proportion of renal interstitial fibrosis area in renal tissue of the model group and the negative control group was higher than that in the miR-223 agonist group and the pathway activation group. The proportion of renal interstitial fibrosis area in renal tissue of the pathway activation group was higher than that in the miR-223 agonist group(P<0.05).The expression levels of IL-6/GAPDH and p-STAT3/STAT3 in the blank group were lower than those in the other four groups. The expression levels of IL-6/GAPDH and pSTAT3/STAT3 in the model group and the negative control group were significantly higher than those in the miR-223 agonist group and the pathway activation group. The expression levels of IL-6/GAPDH and p-STAT3/STAT3 in the pathway activation group were higher than those in the miR-223 agonist group(P<0.05). Conclusion: The expression of inflammatory factors and renal interstitial fibrosis in rats with chronic glomerulonephritis are affected by miR-223. The mechanism may be related to the expression of IL-6/STAT3 signaling pathway-related proteins.展开更多
Objective: To investigate the effects of Yanghe Pingchuan Granules on airway remodeling in asthmatic rats, and to explore the mechanism of Interleukin-6/Janus kinase 2/ Signal transducing activator of transcription 3(...Objective: To investigate the effects of Yanghe Pingchuan Granules on airway remodeling in asthmatic rats, and to explore the mechanism of Interleukin-6/Janus kinase 2/ Signal transducing activator of transcription 3(IL-6/JAK2/STAT3) signal axis. Methods: We separated 42 healthy male SD rats into two groups, a control group (7) and a model group (35).The model group was sensitized with a combination of ovalbumin (OVA) and aluminum hydroxide for 2 weeks, while the control group was given an equal amount of physiological saline.After 2 weeks, the modeling group was randomly divided into Model group, Yanghe Pingchuan Granules high, medium and low dose groups and Dexamethasone group, each group consisted of 7 animals. After 4 weeks, OVA atomization and gavage were used for stimulation and treatment. Yanghe Pingchuan Granules high, middle and low groups were given 15.48, 7.74, 3.87 g∙kg-1 Yanghe Pingchuan Granules daily, dexamethasone group was given 0.0625 mg∙kg-1 dexamethasone daily, and the other groups were given the same amount of normal saline. HE, PAS and Masson staining were used to observe the lung histopathological changes in rats. The levels of interleukin-6, IL-23 and IL-17A were detected by ELISA. The expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 in lung tissues were detected by Western blot. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression levels of IL-6, JAK2 and STAT3 in rat lung tissue. Results: The lung tissue structure of the model group was severely damaged compared to the control group, accompanied by a great many of inflammatory cell infiltration, goblet cell hyperplasia, subepithelial collagen fiber deposition and airway epithelial thickening were more obvious. The expressions of IL-6, IL- 23 and IL-17A in serum were significantly increased (P<0.01), the protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and the mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly increased (P<0.01);Compared with the model group, inflammatory cell infiltration, goblet cell proliferation, subepithelial collagen fiber deposition and airway epithelial thickening were significantly reduced in each administration group, and the expressions of IL-6, IL-23 and IL-17A in serum were significantly decreased (P< 0.01). The protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly decreased (P<0.01). Conclusion: Yanghe Pingchuan Granules can significantly alleviate airway remodeling in asthmatic rats, and its mechanism may be through inhibiting the IL-6/JAK2/STAT3 signal axis.展开更多
Objective:To explore the mechanism of action of Dahuang Lingxian Formula in alleviating the inflammatory response of bile duct cells in LPS-induced intrahepatic bile duct inflammation model rats based on IL-6/JAK/STAT...Objective:To explore the mechanism of action of Dahuang Lingxian Formula in alleviating the inflammatory response of bile duct cells in LPS-induced intrahepatic bile duct inflammation model rats based on IL-6/JAK/STAT3 signaling pathway.Methods:Fifty SD rats were randomly divided into five groups,blank group,model group,choling tablets(0.5 g/kg),and low and high concentration groups(2.4 g/kg and 4.8 g/kg)of Dahuang Lingxian Formula,ten rats in each group.Except for the blank group,the rats in each group were injected with 1.25 mg/kg LPS at the common bile duct at one time to construct an animal model of intrahepatic bile duct infection.After gavage on day 8,liver tissues were taken from rats at the hepatic hilum,and the histopathological changes of the hepatic hilum and biliary tree were observed by HE staining.The expression levels of serum glutamic alanine transaminase(ALT),glutamic oxalacetic transaminase(AST),malondialdehyde(MDA)and superoxide dismutase(SOD)were measured by biochemical method.The expression levels of interleukin 6(IL-6),Janus protein tyrosine kinase 2(JAK2),signal transducer and activator of transcription 3(STAT3)in rat serum were measured by enzyme-linked immunosorbent assay(ELISA).Protein immunoblotting(WB)and real-time fluorescence quantitative PCR(RT-qPCR)were used to detect the expression levels of IL-6,JAK2,STAT3 protein and mRNA in biliary tree tissues.Results:①Compared with the blank group,the structures such as interlobular bile ducts in the hepatic sinusoids and portal duct area of the model rats were destroyed,and inflammatory cells infiltrated around them.The expression of ALT,AST,MDA,IL-6,JAK2 and STAT3 in the serum increased significantly,the expression level of SOD decreased,and the expression levels of IL-6,JAK2 and STAT3 proteins and mRNA increased.②Compared with the model group,the degree of liver pathological damage in rats in the Chiling Ning tablet group and the low and high concentration groups of Dahuang Lingxian Formula were improved,which could significantly reduce the expression levels of ALT,AST,MDA,IL-6,JAK2,STAT3 and up-regulate SOD in serum,and down-regulate the expression of IL-6,JAK2,STAT3 protein and mRNA,with the best effect in the high concentration group of Dahuang Lingxian Formula.③Compared with the choling tablet group,the rats in the low and high concentration groups of Dahuang Lingxian Formula tended to normalize the degree of liver pathological damage,without obvious inflammatory cell infiltration,and the expression levels of ALT,AST,MDA,IL-6,JAK2,STAT3 and the expression levels of IL-6,JAK2,STAT3 protein and mRNA in serum were reduced,and the expression levels of SOD were increased,with the best effect of Dahuang Lingxian Formula The treatment effect was best in the high concentration group.Conclusion:The mechanism may be related to the down-regulation of IL-6/JAK/STAT3 signaling pathway activation,and the best therapeutic effect was achieved by the high concentration group of Dahuang Lingxian Formula.展开更多
基金supported by grants from the Scientific and Technological Research Program of Chongqing Municipal Education Commission(KJ1400220)the Basic Science and Frontier Technology Research Program of Chongqing Science and Technology Commission(cstc2017jcyjAX0224)
文摘Background: Interleukin-37 b(IL-37 b), a vital negative regulator of the innate immune system, has been reported to be a tumor inhibitor in different type of cancers. However, little is known about the relationship between IL-37 b and hepatocellular carcinoma(HCC). The present study aimed to investigate the potential roles of IL-37 b in HCC progression. Methods: Subjects( n = 237) were recruited, and serum IL-37 b was measured using ELISA. The tumorsuppressive capacity and underlying mechanisms of IL-37 b in HCC were investigated in vitro and in vivo. Results: Compared to healthy controls, serum IL-37 b levels were elevated in chronic hepatitis B(CHB) patients but decreased significantly in HBV-HCC patients, especially for those with portal venous tumor thrombus. Low level serum IL-37 b in HBV-HCC patients correlated with high HCC stage and poor overall survival and disease-free survival. In vitro and in vivo, recombinant human IL-37 b inhibited proliferation and metastasis in HCC cells. Furthermore, IL-37 b inhibited epithelial mesenchymal transition in HCC cells in vitro by downregulating IL-6, pSTAT3(Y705), N-cadherin, and vimentin expression and by upregulating E-cadherin expression. These effects were partially reversed by transfection of adenovirus encoding human IL-6. Conclusions: IL-37 b inhibits HCC growth, metastasis and epithelial mesenchymal transition by regulating IL-6/STAT3 signaling. Serum IL-37 b may be a biomarker for HBV-HCC and its staging.
文摘Objective: To explore the effect of miR-223 on the expression of inflammatory factors and renal interstitial fibrosis in a rat model of chronic glomerulonephritis based on the interleukin 6/signal transducer and activator of transcription 3(IL-6/STAT3) signaling pathway. Methods: A total of 70 SPF-grade healthy adult male SD rats were selected, and were randomly divided into five groups. Except for the blank group, the remaining four groups of rats were all subcutaneously injected with 1 mg/m L cationized bovine serum albumin(C-BSA) emulsion at multiple points(in the first week) and injected with 2.5 mg/m L C-BSA solution through the tail vein(from the 2nd to 4th week) to establish a glomerulonephritis model. After successful modeling, the blank group and the modeling group were injected with normal saline through the tail vein, the negative control group was injected with 50 μg/kg NC agomir through the tail vein, the miR-223 agonist group was injected with 50 μg/kg miR-223 agomir through the tail vein, and the pathway activation group was injected with 50 μg/kg miR-223agomir and 1 μg/kg rh IL-6 through the tail vein. After continuous treatment for 21 d,the rats were sacrificed and kidney tissues were taken. The expression of miR-223, inflammatory factors and IL-6/STAT3 signaling pathway-related proteins in the five groups of rats was observed and compared, and the renal interstitial fibrosis in the five groups of rats was also observed and compared. Results: The relative expression level of miR-223 in the blank group was significantly higher than that in the other four groups. The relative expression levels of miR-223 in the miR-223 agonist group and the pathway activation group were significantly higher than those in the model group and the negative control group(P<0.05). The expression levels of IL-1β, IL-17, TNF-α, and TGF-β1 in the blank group were lower than those in the other four groups. The expression levels of IL-1β, IL-17, TNF-α, and TGF-β1 in the model group and the negative control group were significantly higher than those in the miR-223 agonist group and the pathway activation group. The expression levels of IL-1β, IL-17, TNF-α,and TGF-β1 in the pathway activation group were higher than those in the miR-223agonist group(P<0.05). The proportion of renal interstitial fibrosis area in renal tissue of the blank group was significantly lower than that in the other four groups. The proportion of renal interstitial fibrosis area in renal tissue of the model group and the negative control group was higher than that in the miR-223 agonist group and the pathway activation group. The proportion of renal interstitial fibrosis area in renal tissue of the pathway activation group was higher than that in the miR-223 agonist group(P<0.05).The expression levels of IL-6/GAPDH and p-STAT3/STAT3 in the blank group were lower than those in the other four groups. The expression levels of IL-6/GAPDH and pSTAT3/STAT3 in the model group and the negative control group were significantly higher than those in the miR-223 agonist group and the pathway activation group. The expression levels of IL-6/GAPDH and p-STAT3/STAT3 in the pathway activation group were higher than those in the miR-223 agonist group(P<0.05). Conclusion: The expression of inflammatory factors and renal interstitial fibrosis in rats with chronic glomerulonephritis are affected by miR-223. The mechanism may be related to the expression of IL-6/STAT3 signaling pathway-related proteins.
基金The Sixth Batch of Special Support Plans in Anhui Province(No.dlPtzjh20200050)Key Natural Science Research Project of Higher Education Institutions in Anhui Province(No.KJ2020A0426)。
文摘Objective: To investigate the effects of Yanghe Pingchuan Granules on airway remodeling in asthmatic rats, and to explore the mechanism of Interleukin-6/Janus kinase 2/ Signal transducing activator of transcription 3(IL-6/JAK2/STAT3) signal axis. Methods: We separated 42 healthy male SD rats into two groups, a control group (7) and a model group (35).The model group was sensitized with a combination of ovalbumin (OVA) and aluminum hydroxide for 2 weeks, while the control group was given an equal amount of physiological saline.After 2 weeks, the modeling group was randomly divided into Model group, Yanghe Pingchuan Granules high, medium and low dose groups and Dexamethasone group, each group consisted of 7 animals. After 4 weeks, OVA atomization and gavage were used for stimulation and treatment. Yanghe Pingchuan Granules high, middle and low groups were given 15.48, 7.74, 3.87 g∙kg-1 Yanghe Pingchuan Granules daily, dexamethasone group was given 0.0625 mg∙kg-1 dexamethasone daily, and the other groups were given the same amount of normal saline. HE, PAS and Masson staining were used to observe the lung histopathological changes in rats. The levels of interleukin-6, IL-23 and IL-17A were detected by ELISA. The expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 in lung tissues were detected by Western blot. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression levels of IL-6, JAK2 and STAT3 in rat lung tissue. Results: The lung tissue structure of the model group was severely damaged compared to the control group, accompanied by a great many of inflammatory cell infiltration, goblet cell hyperplasia, subepithelial collagen fiber deposition and airway epithelial thickening were more obvious. The expressions of IL-6, IL- 23 and IL-17A in serum were significantly increased (P<0.01), the protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and the mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly increased (P<0.01);Compared with the model group, inflammatory cell infiltration, goblet cell proliferation, subepithelial collagen fiber deposition and airway epithelial thickening were significantly reduced in each administration group, and the expressions of IL-6, IL-23 and IL-17A in serum were significantly decreased (P< 0.01). The protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly decreased (P<0.01). Conclusion: Yanghe Pingchuan Granules can significantly alleviate airway remodeling in asthmatic rats, and its mechanism may be through inhibiting the IL-6/JAK2/STAT3 signal axis.
基金Guangxi Natural Science Foundation(No.2020GXNSFAA238012)Research on Traditional Chinese Medicine Prevention and Treatment of Liver and Bile Related Diseases in the 2021"Qihuang Project"High Level Talent Team Cultivation Project(No.2021006)+1 种基金2020 Guangxi University of Traditional Chinese Medicine First Affiliated Hospital Hospital Hospital Level Doctoral Initiation Fund Project(No.2020BS004)2020 Guangxi University of Traditional Chinese Medicine Introduction Doctoral Research Initiation Fund Project(No.2020BS030)。
文摘Objective:To explore the mechanism of action of Dahuang Lingxian Formula in alleviating the inflammatory response of bile duct cells in LPS-induced intrahepatic bile duct inflammation model rats based on IL-6/JAK/STAT3 signaling pathway.Methods:Fifty SD rats were randomly divided into five groups,blank group,model group,choling tablets(0.5 g/kg),and low and high concentration groups(2.4 g/kg and 4.8 g/kg)of Dahuang Lingxian Formula,ten rats in each group.Except for the blank group,the rats in each group were injected with 1.25 mg/kg LPS at the common bile duct at one time to construct an animal model of intrahepatic bile duct infection.After gavage on day 8,liver tissues were taken from rats at the hepatic hilum,and the histopathological changes of the hepatic hilum and biliary tree were observed by HE staining.The expression levels of serum glutamic alanine transaminase(ALT),glutamic oxalacetic transaminase(AST),malondialdehyde(MDA)and superoxide dismutase(SOD)were measured by biochemical method.The expression levels of interleukin 6(IL-6),Janus protein tyrosine kinase 2(JAK2),signal transducer and activator of transcription 3(STAT3)in rat serum were measured by enzyme-linked immunosorbent assay(ELISA).Protein immunoblotting(WB)and real-time fluorescence quantitative PCR(RT-qPCR)were used to detect the expression levels of IL-6,JAK2,STAT3 protein and mRNA in biliary tree tissues.Results:①Compared with the blank group,the structures such as interlobular bile ducts in the hepatic sinusoids and portal duct area of the model rats were destroyed,and inflammatory cells infiltrated around them.The expression of ALT,AST,MDA,IL-6,JAK2 and STAT3 in the serum increased significantly,the expression level of SOD decreased,and the expression levels of IL-6,JAK2 and STAT3 proteins and mRNA increased.②Compared with the model group,the degree of liver pathological damage in rats in the Chiling Ning tablet group and the low and high concentration groups of Dahuang Lingxian Formula were improved,which could significantly reduce the expression levels of ALT,AST,MDA,IL-6,JAK2,STAT3 and up-regulate SOD in serum,and down-regulate the expression of IL-6,JAK2,STAT3 protein and mRNA,with the best effect in the high concentration group of Dahuang Lingxian Formula.③Compared with the choling tablet group,the rats in the low and high concentration groups of Dahuang Lingxian Formula tended to normalize the degree of liver pathological damage,without obvious inflammatory cell infiltration,and the expression levels of ALT,AST,MDA,IL-6,JAK2,STAT3 and the expression levels of IL-6,JAK2,STAT3 protein and mRNA in serum were reduced,and the expression levels of SOD were increased,with the best effect of Dahuang Lingxian Formula The treatment effect was best in the high concentration group.Conclusion:The mechanism may be related to the down-regulation of IL-6/JAK/STAT3 signaling pathway activation,and the best therapeutic effect was achieved by the high concentration group of Dahuang Lingxian Formula.
文摘溃疡性结肠炎(ulcerative colitis,UC)是一种因多种因素导致肠黏膜屏障受损,进而引发肠黏膜持续性炎症损伤的复发性炎症性肠病(inflammatory bowel disease,IBD),以炎症局限于黏膜与黏膜下层为特征,病变多自直肠开始,逆行累及全结肠甚至末端回肠。目前病因未明,已有研究表明炎症介质和细胞信号通路的异常激活在UC发展中可能起重要作用,其中,白细胞介素-6/信号传导及转录激活因子3(interleukin-6/signal transducer and activator of transcription 3,IL-6/STAT3)信号通路是UC发展过程中的关键信号通路。研究表明,中医药可通过对IL-6/STAT3信号通路进行干预,发挥其抗炎、调节免疫损伤以及调节胃肠道菌群失调的作用,从而达到改善肠道黏膜损伤、减轻肠道炎症的目的。文章总结近年来的相关研究,探讨中医药通过调节IL-6/STAT3信号通路治疗UC的进展,以期为UC的防治提供新思路。
