一氧化氮與前腺素E2在免疫及發炎反應中扮演重要角色。一氧化氮由一氧化氮合成脢催化產生。一氧化氮合成與前腺素E2訊息徑之間的交互作用，涉及複雜機轉。在此份研究計劃中，我們探討一氧化氮與前腺素E2及其之間交互作用在腎臟絲球體細胞中環腺甘酸訊息徑所扮演之角色，以瞭解二者之間的交互作用，如何誘發腎絲球體腎炎之致病機轉。我們的實驗結果顯示，在腎臟絲球體細胞中，外加入前腺素E2及環腺甘酸可以加強內毒素及干擾素誘發之一氧化氮生成。此外，在腎臟絲球體細胞中加以一氧化氮捐貢者(GEA 3162)，導致前腺素E2誘發之下游環腺甘酸反應下。
The role of nitric oxide (NO) and prostaglandin E2 (PGE2) in mediating immune response have been well documented. NO, generated from L-arginine, is the product of nitric oxide synthase (NOS). The interaction between NO biosynthesis and PGE2 signaling pathway was intricate. Preliminary data indicated both PGE2 and dibutyryl cyclic AMP (db-cAMP), a cell-permeable derivative of cAMP, stimulated the production of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS) in the SV40-transformed mouse mesangial (MES-13) cells. Incubation of MES-13 cells with db-cAMP alone did not produce NO and induce iNOS expression. The combination of lipopolysaccharide (LPS) with db-cAMP greatly enhanced NO production in a synergistic pattern, and led to induction of iNOS expression, both in mRNA and protein level. Prostaglandin E2 (PGE2), known to be an intracellular physiological trigger of cAMP formation, stimulated no inducible iNOS when added alone or with LPS. Induction of NO production and iNOS expression by PGE2 were only observed in response to LPS + interferon-gamma (IFN-gamma) in MES-13 cells. Our data indicated PGE2 as a co-stimulatory factor amplifying LPS + IFN-gamma -induced iNOS gene expression and subsequent NO synthesis in MES-13
