G2A Regulates Macrophage Differentiation

Multiple sclerosis (MS) is one of the most common diseases in demyelinating disease of the central nervous system. Its main feature is the pathological changes of demyelination in central nervus system. Macrophages and other immune cells plays an important role in that. When Ml macrophage transfer to M2 macrophage, the M2 macrophages which has anti-inflammatory effects can ease the development of the disease and control the CNS inflammation to promote and repair the damaged tissue. It is obviously that the ratio of human M1,M2 macrophage is very important for the development of this chronic disease and CNS tissue repair. LP-PLA2 is secreted by the monocyte derived macrophages, T lymphocytes, mast cells. LP-PLA2 oxidative cleavage phosphatidylcholine, generating lysophosphatidylcholine (lysoPC) oxidized non-esterified fatty acids (NEFAs), 9-hydroxyoctadecadienoic acid (HODE) in tissues. It is involved in the regulation of many immune-related diseases,through its G2A receptor. G2A is a G protein-coupled receptors and it's highly expressed in macrophages, especially in the peripheral blood mononuclear cell (PBMC) of MS patient's blood. That means G2A+ macrophages, monocytes, Microglia plays an important role in the pathogenesis of MS. We found that after rats injected with LP-PLA2 inhibitors and G2A antibodies, the symptoms of immunized EAE rats was eased. Then we conducted the frozen section and western blotting to the brain of those rats. The improvement was mainly due to G2 A regulated the proportion of macrophages. Beside that we also found the LP-PLA2-lysoPC-G2A-SRC-STAT5-IRF5 this new signaling pathway.We found out that the inhibition G2A can inhibit the differentitation of Ml-type macrophage, thereby adjusting the ratio of Ml, M2 type macrophage. So it has a very significant meaning for the treatment of MS. Experimental autoimmune encephalomyelitis (experimental autoimmune encephalomyelitis, EAE) is an ideal animal model of human MS, which is highly similar to the pathogenesis of MS.Experiments shows that in experimental autoimmune encephalomyelitis(EAE) animal model...