Cytokines are secreted by various cell types and act as critical mediators in many physiological processes,including immune response and tumor progression.Cytokines production is precisely and timely regulated by mult...Cytokines are secreted by various cell types and act as critical mediators in many physiological processes,including immune response and tumor progression.Cytokines production is precisely and timely regulated by multiple mechanisms at different levels,ranging from transcriptional to post-transcriptional and posttranslational processes.Monocyte chemoattractant protein-1 induced protein 1(MCPIP1),a potent immunosuppressive protein,was first described as a transcription factor in monocytes treated with monocyte chemoattractant protein-1(MCP-1)and subsequently found to possess intrinsic RNase and deubiquitinase activities.MCPIP1 tightly regulates cytokines expression via various functions.Furthermore,cytokines such as interleukin 1 beta(IL-1B)and MCP-1 and inflammatory cytokines inducer lipopolysaccharide(LPS)strongly induce MCPIP1 expression.Mutually regulated MCPIP1 and cytokines form a complicated network in the tumor environment.In this review,we summarize how MCPIP1 and cytokines reciprocally interact and elucidate the effect of the network formed by these components in cancer-related immunity with aim of exploring potential clinical benefits of their mutual regulation.展开更多
MCP-1-induced protein-1(MCPIP1)is a newly identified protein that is crucial to immune regulation.Mice lack-ing MCPIP1 gene suffer from severe immune disorders,and most of them cannot survive longer than 12 weeks.Cons...MCP-1-induced protein-1(MCPIP1)is a newly identified protein that is crucial to immune regulation.Mice lack-ing MCPIP1 gene suffer from severe immune disorders,and most of them cannot survive longer than 12 weeks.Considerable progress has been made in revealing the mechanism underlying the immune regulatory function of MCPIP1.MCPIP1 can act as an RNase to promote the mRNA degradation of some inflammatory cytokines,such as IL-6 and IL-1.Pre-microRNAs are also confirmed to be the substrate of MCPIP1 RNase.The structure of MCPIP1 N-terminal conserved domain shows a PilT N-terminus-like RNase structure,further supporting the notion that MCPIP1 has RNase activity.MCPIP1 can also deubiquitinate TNF receptor-associated factor family proteins,which are known to mediate immune and inflammatory responses.In this review,we summarize recent progress on the immune regulatory role of MCPIP1 and discuss the mechanisms underlying its function.展开更多
Background:Mounting evidence,consistent with our previous study,showed thatγ-aminobutyric acid type A receptor(GABAAR)played an indispensable role in airway inflammation and mucus hypersecretion in asthma.Monocyte ch...Background:Mounting evidence,consistent with our previous study,showed thatγ-aminobutyric acid type A receptor(GABAAR)played an indispensable role in airway inflammation and mucus hypersecretion in asthma.Monocyte chemotactic protein-inducing protein 1(MCPIP1)was a key negative regulator of inflammation.Recent studies showed that inflammation was largely suppressed by enhanced MCPIP1 expression in many inflammatory diseases.However,the role and potential mechanism of MCPIP1 in airway inflammation and mucus hypersecretion in asthma were still not well studied.This study was to explore the role of MCPIP1 in asthmatic airway inflammation and mucus hypersecretion in both mice and BEAS-2B cells,and its potential mechanism.Methods:In vivo,mice were sensitized and challenged by ovalbumin(OVA)to induce asthma.Airway inflammation and mucus secretion were analyzed.In vitro,BEAS-2B cells were chosen.Interleukin(IL)-13 was used to stimulate inflammation and mucus hypersecretion in cells.MCPIP1 Lentiviral vector(LA-MCPIP1)and plasmid-MCPIP1 were used to up-regulate MCPIP1 in lung and cells,respectively.MCP-1,thymic stromal lymphopoietin(TSLP),mucin 5AC(MUC5AC),MCPIP1,and GABAARβ2 expressions were measured in both lung and BEAS-2B cells.Immunofluorescence staining was performed to observe the expression of GABAARβ2 in cells.Results:MCPIP1 was up-regulated by LA-MCPIP1(P<0.001)and plasmid-MCPIP1(P<0.001)in lung and cells,respectively.OVA-induced airway inflammation and mucus hypersecretion,OVA-enhanced MCP-1,TSLP,MUC5AC,and GABAARβ2 expressions,and OVA-reduced MCPIP1 were significantly blunted by LA-MCPIP1 in mice(all P<0.001).IL-13-enhanced MCP-1,TSLP,MUC5AC,and GABAARβ2 expressions,and IL-13-reduced MCPIP1 were markedly abrogated by plasmid-MCPIP1 in BEAS-2B cells(all P<0.001).Conclusion:The results of this study suggested that OVA and IL-13-induced airway inflammation and mucus hypersecretion were negatively regulated by MCPIP1 in both lung and BEAS-2B cells,involving GABAAR signaling pathway.展开更多
基金This work was supported by the Funds for the National Natural Science Foundation of China(Grant No.81700201)Zhejiang Key Research and Development Project(2020C03014)National Major Scientific and Tech no logical Special Project for"Sig nifica nt New Drug Development"(2018ZX09733-003).
文摘Cytokines are secreted by various cell types and act as critical mediators in many physiological processes,including immune response and tumor progression.Cytokines production is precisely and timely regulated by multiple mechanisms at different levels,ranging from transcriptional to post-transcriptional and posttranslational processes.Monocyte chemoattractant protein-1 induced protein 1(MCPIP1),a potent immunosuppressive protein,was first described as a transcription factor in monocytes treated with monocyte chemoattractant protein-1(MCP-1)and subsequently found to possess intrinsic RNase and deubiquitinase activities.MCPIP1 tightly regulates cytokines expression via various functions.Furthermore,cytokines such as interleukin 1 beta(IL-1B)and MCP-1 and inflammatory cytokines inducer lipopolysaccharide(LPS)strongly induce MCPIP1 expression.Mutually regulated MCPIP1 and cytokines form a complicated network in the tumor environment.In this review,we summarize how MCPIP1 and cytokines reciprocally interact and elucidate the effect of the network formed by these components in cancer-related immunity with aim of exploring potential clinical benefits of their mutual regulation.
基金supported by grants from the National Basic Research Program(973 Program)(Nos.2011CB915501 and 2011CB910304).
文摘MCP-1-induced protein-1(MCPIP1)is a newly identified protein that is crucial to immune regulation.Mice lack-ing MCPIP1 gene suffer from severe immune disorders,and most of them cannot survive longer than 12 weeks.Considerable progress has been made in revealing the mechanism underlying the immune regulatory function of MCPIP1.MCPIP1 can act as an RNase to promote the mRNA degradation of some inflammatory cytokines,such as IL-6 and IL-1.Pre-microRNAs are also confirmed to be the substrate of MCPIP1 RNase.The structure of MCPIP1 N-terminal conserved domain shows a PilT N-terminus-like RNase structure,further supporting the notion that MCPIP1 has RNase activity.MCPIP1 can also deubiquitinate TNF receptor-associated factor family proteins,which are known to mediate immune and inflammatory responses.In this review,we summarize recent progress on the immune regulatory role of MCPIP1 and discuss the mechanisms underlying its function.
基金supported by grants from the National Natural Science Foundation of China for Young Scholar(No.81801484)China Postdoctoral Science Foundation(No.2014M552369)+1 种基金Natural Science Foundation of Guangdong Province(No.2017A030310286)Scientific Research Project of Guangzhou(No.201707010282)。
文摘Background:Mounting evidence,consistent with our previous study,showed thatγ-aminobutyric acid type A receptor(GABAAR)played an indispensable role in airway inflammation and mucus hypersecretion in asthma.Monocyte chemotactic protein-inducing protein 1(MCPIP1)was a key negative regulator of inflammation.Recent studies showed that inflammation was largely suppressed by enhanced MCPIP1 expression in many inflammatory diseases.However,the role and potential mechanism of MCPIP1 in airway inflammation and mucus hypersecretion in asthma were still not well studied.This study was to explore the role of MCPIP1 in asthmatic airway inflammation and mucus hypersecretion in both mice and BEAS-2B cells,and its potential mechanism.Methods:In vivo,mice were sensitized and challenged by ovalbumin(OVA)to induce asthma.Airway inflammation and mucus secretion were analyzed.In vitro,BEAS-2B cells were chosen.Interleukin(IL)-13 was used to stimulate inflammation and mucus hypersecretion in cells.MCPIP1 Lentiviral vector(LA-MCPIP1)and plasmid-MCPIP1 were used to up-regulate MCPIP1 in lung and cells,respectively.MCP-1,thymic stromal lymphopoietin(TSLP),mucin 5AC(MUC5AC),MCPIP1,and GABAARβ2 expressions were measured in both lung and BEAS-2B cells.Immunofluorescence staining was performed to observe the expression of GABAARβ2 in cells.Results:MCPIP1 was up-regulated by LA-MCPIP1(P<0.001)and plasmid-MCPIP1(P<0.001)in lung and cells,respectively.OVA-induced airway inflammation and mucus hypersecretion,OVA-enhanced MCP-1,TSLP,MUC5AC,and GABAARβ2 expressions,and OVA-reduced MCPIP1 were significantly blunted by LA-MCPIP1 in mice(all P<0.001).IL-13-enhanced MCP-1,TSLP,MUC5AC,and GABAARβ2 expressions,and IL-13-reduced MCPIP1 were markedly abrogated by plasmid-MCPIP1 in BEAS-2B cells(all P<0.001).Conclusion:The results of this study suggested that OVA and IL-13-induced airway inflammation and mucus hypersecretion were negatively regulated by MCPIP1 in both lung and BEAS-2B cells,involving GABAAR signaling pathway.
