Effect And Mechanism Of GLP-2 On Activation Of Microglia Induced By LPS

Parkinson’s disease is a common degenerative disease of the nervous tissue.The main cause of the disease is the substantia nigra dopaminergic neurons injury zone.Its main features include short slowness of movement, muscle rigidity, walking chaos. Recent years, more and more researches on PD have shown that nerve inflammation plays a crucial role in the occurrence and development of PD. In the process of nerve inflammation, microglia are the main effector cells. Current studies suggest that excessive activation of microglia can produce a large number of pro-inflammatory factors and these cytokines can cause excessive inflammation and ultimately lead to damage to dopamine neurons and trigger PD. Although we now have a clear and inflammatory response related to the pathogenesis of PD, but the mechanism is not clear. Therefore, inhibit the nerve inflammation may be called a critical step in the treatment of PD.Glucagon like peptide-2（GLP-2） consisting of 33 amino acids is a polypeptide substance released by the intestinal mucosal endocrine L cells.This small molecular polypeptide is mainly found in the ileum and colon.GLP-2 can play a wide variety of biological characteristics and role through its receptor GLP-2R, such as promoting the protection of small intestine, repair the damaged intestinal mucosa, promote the growth and development of intestinal mucosa and increase the intestinal blood flow.which includes effective inhibition of inflammation. Especially in recent years, it is found that it plays a very important role in anti inflammation, The anti-inflammatory effect of GLP-2 has been confirmed in the peripheral tissues and organs.The anti-inflammatory effect of GLP-2 has been confirmed in the peripheral tissues and organs and more research shows that it has obvious anti-inflammatory effect on activated peritoneal macrophages.Therefore, this study explored the anti-inflammatory effect and mechanism of GLP-2 on the activated microglia cell line BV-2 in order to reveal GLP-2 for potential therapeutic role for neuroinflammation and PD. First of all, BV-2 cells were pretreated with different concentrations of GLP-2(10^-9、10^-8、10^-7、10^-6M), and then stimulated by lipopolysaccharide（LPS）. The effects of GLP-2 on the inflammatory response were assessed by the detection of inflammatory cytokines（i NOS and COX-2） and proinflammatory cytokines（IL-1β, TNF- α, and IL-6）.And then we use PCR to detect whether there is GLP-2 receptor（GLP-2R） in the BV-2. After that, we also detect the phosphorylation levels of the key factors in the MAPKs and NF- κ B inflammatory signaling pathways in order to study the mechanism of the anti-inflammatory function of GLP-2. The results showed that GLP-2 significantly reduced the content of i NOS, COX-2, IL-1β, IL-6 and TNF-αafter induction of LPS. The expression of GLP-2 receptor（GLP-2R） was not found in the microglia cell line after BV-2 was detected by PCR. However, use a kind of G alpha s protein coupled receptor blocking agent-NF449 to treatment BV-2 can significantly inhibit the anti-inflammatory effect of GLP-2. Western blotting results showed that GLP-2 decreased ERK1/2, JNK and p65 phosphorylation induced by LPS, but had no significant effect on p38 phosphorylation.All the results collectively suggest that GLP-2 through regulating ERK, JNK and p65 phosphorylation inhibited LPS induced microglial cell activation, so as to achieve the effect of inhibiting inflammation.