The Role Of Gαq In Macrophage Inflammatory Response And The Pathogenesis Of Ulcerative Colitis

Ulcerative colitis is a chronic intestinal inflammatory disease.The main clinical manifestations of ulcerative colitis are abdominal pain,loose stools,and blood stool.The pathogenesis of ulcerative colitis has not been fully elucidated,and it is generally thought that genetic factors,infection factors,environmental factors and immune factors are closely related to the pathogenesis of ulcerative colitis.Among them,immune factors have been the focus of research.Macrophage is an important innate immune cell,and identified PAMPs and DAMPs signals through the PRR on the cell surface,which in turn trigger a series of immune responses.Numerous experiments have shown that macrophage play a crucial role in the development of ulcerative colitis.Macrophages can participate in the pathogenesis of ulcerative colitis by secreting pro-inflammatory cytokines such as IL-6、TNF-α.Abnormal activation and function of macrophages can be detected during the development of ulcerative colitis.The G protein signaling system is an important signal transduction system in mammals.G Protein Coupled Receptors（GPCRs）can transduces a large of extracellular signals which combination to G proteins,such as hormones,neurotransmitters,chemokines and sensory stimuli.The G protein can transform these extracellular signals into cellular responses and regulate multiple biological functions.The G protein consists of three subunits:α、βandγ.Theαsubunit of G protein can induce different downstream signals.Depending on the downstream signal ofαsubunit,G protein can be divided into four subfamilies:Gs,Gi,Gq/11 and G12/13.Gq is an important member of the Gq/11 subfamily,the functional unit of its alpha subunit is Gαq,and Gαq is encoded by the Gnaq gene.Some studies have shown that Gαq proteins play an important role in nervous system,endocrine system and cardiovascular system.In recent years,the critical role of Gαq in immune system attracts a lot of interest.Previous study has found that Gαq knockout(Gnaq^-/-)mouse T cells had significant survival advantages in vitro and in vivo.A recent research showed that Gαq can regulate the differentiation of Th1 and Th17 cells.These results indicate that the Gαq protein plays a crucial role in immune function of T cells.Since Gαq has important immune regulatory functions and macrophages secreted pro-inflammatory cytokines play an important role in the pathogenesis of ulcerative colitis,Gαq may be involved in the pathogenesis of ulcerative colitis by regulating macrophage inflammatory response.Therefore,this study will investigate the role of Gαq on macrophage inflammatory response and the pathogenesis of ulcerative colitis.We used DSS to induce Gnaq^+/-mice and WT mice to develop ulcerative colitis,compared the incidence of the two genotype mice,and assessed the degree of colon damage by pathological sections.We also detected the secretion of IL-6 and TNF-αin mouse colon tissue by ELISA.And,we isolated and cultured bone marrow derived macrophages from WT and Gnaq^-/-mice.After stimulated by LPS,the secretion of IL-6and TNF-αin cell culture supernatant was detected by ELISA.Results showed that Gnaq^+/-mice were more prone to develop DSS-induced ulcerative colitis.Pathological sections showed that the histological score of Gnaq^+/-mice was significantly higher than that of WT mice,and the expression of IL-6 and TNF-αin colon homogenate was also significantly increased.After stimulated by LPS,the secretion of IL-6,TNF-αwere significantly increased in culture supernatant of Gnaq^-/-bone marrow derived macrophages.These results indicated that Gαq may be involved in macrophage inflammatory response and the pathogenesis of ulcerative colitis.