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¹ Laboratory of Reproductive Endocrinology, Graduate School of Natural Science and Technology, Okayama University, Okayama 700-8530, Japan² Division of Applied Life Science, Graduate School of Integrated Science and Art, University of East Asia, Shimonoseki, Yamaguchi 751-8503, Japan³ Department of Reproductive Immunology, Institute of Animal Reproduction & Food Research, Polish Academy of Sciences, Olstzyn 10-747, Poland⁴ National Institute of Animal Science, Suwon 441-706, South Korea⁵ Department of Animal Biotechnology, College of Animal Life Science, Kangwon National University, Chunchon 200-701, South Korea⁶ School of Life Sciences & Biotechnology, College of Natural Sciences, Kyungpook National University, Daegu 702-701, South Korea

(Correspondence should be addressed to T J Acosta; Email: acosta{at}cc.okayama-u.ac.jp)

Interleukin-1 (IL1) has been shown to be a potent stimulator of prostaglandin (PG) production in bovine endometrium. The aim of the present study was to determine the cell types in the endometrium (epithelial or stromal cells) responsible for the secretion of PGE2 and PGF2 in response to IL1A, and the intracellular mechanisms of IL1A action. Cultured bovine epithelial and stromal cells were exposed to IL1A or IL1B (0.006–3.0 nM) for 24 h. IL1A and IL1B dose-dependently stimulated PGE2 and PGF2 production in the stromal cells, but not in the epithelial cells. The stimulatory effect of IL1A (0.06–3.0 nM) on PG production was greater than that of IL1B. The stimulatory actions of IL1A on PG production was augmented by supplementing arachidonic acid (AA). When the stromal cells were incubated with IL1A and inhibitors of phospholipase (PL) C or PLA2 (1 µM; anthranilic acid), only PLA2 inhibitor completely stopped the stimulatory action of IL1A on PG production. Moreover, a specific cyclooxygenase-2 (COX2) inhibitor blocked the stimulatory effect of IL1A on PG production. IL1A (0.06 nM) promoted COX2 and microsomal PGE synthase-1 (PGES1) gene and its protein expression. The expression of COX1, PGES2, PGES3, and PGF synthase (PGFS) mRNA was not affected by IL1A in the stromal cells. The overall results indicate that 1) the target of IL1A and IL1B for stimulating both PGE2 and PGF2 production is the stromal cells, 2) IL1A is a far more potent stimulator than IL1B on PG production in stromal cells, 3) the stimulatory effect of IL1A on PG production is mediated via the activation of PLA2 and COX2, and (4) IL1A induced PG production by increasing expressions of COX2 and PGES1 mRNAs and their proteins in bovine stromal cells.