The Production of Prostaglandin , Thromboxane and Cytokines in Human Term Decidual Cell Fraction by NG-nitro-L-arginine methyl ester Stimulation

Park, M H; Kim, Y K; Chun, S H; Kim, J I; Ahn, J J; Seo, J Y

Abstract

BACKGROUND: The mechanism that maintains relative uterine quiescence during pregnancy remains almost unknown, but probably involves a complex balance of inhibitory and stimulatory factors. In the last few years, a possible role for nitric oxide[NO], a potent inhibitor of smooth muscle contraction, has emerged. NO is a potent endogenous smooth muscle relaxant. It is synthesized from L-arginine by nitric oxide synthases[NOS]. Prostanoids including prostaglandin[PG] and thromboxane[TX], play a role in the regulation of parturition by stimulating uterine contractility and causing cervical ripening. In addition, a number of cytokines induce decidual prostaglandin output, which suggests that these cytokines have a role to play in labour. But interaction between NO, Prostanoid and cytokines pathways has not been elucidated in human decidua during pregnancy and parturition. Human decidua in the third trimester of pregnancy contains heterogenous cell types. The contributions of these cells to the overall function of the tissue are not known and the cellular source of decidual produced cytokines has not been identified. OBJECTIVE: The purpose of this study was to investigate the possible interrelationship between NO, prostanoids and cytokines in human term decidual cell fraction and to identify cellular origin of decidual cytokines.
METHODS
We investigated the changes of PGE2, TXB2 and cytokines production by decidual cells stimulated with NG-nitro-L-arginine methyl ester[L-NAME], and identified cellular origin of decidula cytokine through flow cytometry.
RESULTS
1. The production of prostaglandin E2 and thromboxane B2 by decidual cell fraction after incubation with L-NAME showed no difference with control group. 2. Increased IL-1 expression and production were demonstrated on decidual cell fraction after incubation with L-NAME. 3. The production of IL-8 by decidual cell fraction after incubation with L-NAME showed no difference with controls but IL-8 was markedly stimulated by not specific stimulies at control group. 4. It were CD 14 positive decidual cells[macrophages] that cellular origin of cytokines among various human decidual cells.
CONCLUSIONS
NO modulates directly decidual IL-1 expression and production, but NO does not modulate directly on production of PGE2, TXB2 and IL-8, suggesting NO may acts indirectly on production of PGE2, TXB2 and IL-8 through regulatory factors such as IL-1. And activation of macrophages from decidual cell fraction may be an important factor in initiation of labor based on our result that proved macrephage to be cell that produces important cytokines such as IL-1 and IL-8 on labor.