The GABAergic System Participates The Antigen-presenting Of DCs In The Intestinal Mucosa And Plays A Role In The DSS-induced Enteritis

Introduction y-aminobutyric acid(GABA), the principal inhibitory neurotransmitter in the mammalian central nervous system (CNS), mediates the fast inhibiton of neurons, and is widely distributed in the brain and spinal cord. Physiologically, GABA is synthesized by glutamate decarboxylase(GAD) from glutamate in neurons which are called GABAergic neurons. GABA prmarily plays a specific role in body by binding to GABA receptors There are three types of GABA repceptors including GABAA receptor,GABAB receptor and GABAc repceptor. GABAA repceptors are chloride ion channels. GABA inhibitory neurotransmission is essential in normal brain function, in neuronal activity, information processing and plasticity, and network synchronization,and in disease. GABAergic medications are used to treat anxiety, alcohol withdrawal, epilepsy, and to induce sedation, and anesthesia.Besides CNS, GABAergic signal system is found in many peripheral tissues and organs like lungs, reproductive system, kidney as well as gastrointestinal tract. In addition to its well-known CNS roles, GABA also modulates inflammation. GABA receptor transcripts are present in immune cells. GABA treatment decreases inflammatory cytokine production in peripheral macrophages. GABA and GABA type A receptor (GABA-A-R) agonists decrease cytotoxic immune responses and cutaneous delayed-type hypersensitivity reactions.Dendritic cells (DCs) are antigen-presenting cells that play an essential role in mucosal tolerance. They regularly encounter beneficial intestinal bacteria, but the nature of these cellular contacts and the immune responses elicited by the bacteria are not entirely elucidated. Some reports have proved the interactions of intestinal bacteria, such as Lactobacillus acidophilus NCFM and its cell surface compounds with DCs, and also been proved that the bacterium binds to DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN), a DC-specific receptor. DC-SIGN as a pattern recognition receptor, plays an important role in mediating DC adhesion, migration, inflammation, activating primary T cell,triggering immune response and participating in immune escape of pathogens and tumors.Inflammatory bowel disease(IBD) is a chronic inflammatory disease of the gastrointestial tract. Its main clinical manifestations are abdominal pain and diarrhea. Its etiology is complicated. Currently genetic suscepitbility, mucosal immunity and the gut microflora environment, as the interaction of the three main elements, are thought to be participating in the pathogenesis of IBD. Probiotic bactera group in the gut, such as bifidobacterium and Lactobacillus, paly an impportant physiological functions in maintaining normal intestinal flora balance, improving the immune capacity, promoting the absorption of nutrients, as well as inhibition of intestinal pathogens and other aspects. Many studies have shown that the interaction of gut bacteria and the immune system in the pathogenesis of IBD plays an important role.Objectives The research background above mentioned promoted us to further explore the possibility that the GABAergic system participates the antigen-presenting of DCs in the intestinal mucosa. And we also examine the roleof GABA ergic in the DSS-induced enteritis.Methods iDCs derived from mouse myeloid was used. Western Blot technique was used to evaluate the expression of the GABAergic system in DCs. The FITC-labeled beneficial intestinal bacteria, Lactobacillus crispatus and pathogenic bacteria Slamonella were used.We detected the role of GABA or specific GABAA receptor agonist on adhesion between DCs and FITC-labeled bacteria.,Using the Western Blot technique, we examined the role of GABA on the expression of DC-SIGN protein in DCs. At last, we established the dextran sulfate sodiμm(DSS)-induced colitis in C57BL/6 male mice. The body weight, blood in the stool,and the MPO activity were measured. Then, the colon of each animal was sectioned with paraffin slices set for a thickness of 4μm. The sections from colon were stained for hematoxylin/eosin.Results We found tha the expression of the GABAergic system existed in the DCs, andGABA inhibited the adhesion between DCs and the intestinal beneficial bacteria Lactobacillus crispatus by GABAA receptors, but improved the adhesion of pathogenic bacteria Slamonella with DCs. GABAergic system also participate the the forming process of ulcerative colitis in mice.Conclusions GABAergic system participates the antigen-presenting of DCs in the intestinal mucosa, and plays a significant role in DSS-induced enteritis.