Takahashi Hideo K, Iwagaki Hiromi, Tamura Ryuji, Katsuno Goutaro, Xue Dong, Sugita Sachi, Mori Shuji, Yoshino Tadashi, Tanaka Noriaki, Nishibori Masahiro
Department of Pharmacology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Eur J Pharmacol. 2005 Apr 11;512(2-3):223-30. doi: 10.1016/j.ejphar.2005.01.046.
The effect of prostaglandins E1 and E2 on the 1 ng/ml lipopolysaccharide-induced expression of intercellular adhesion molecule (ICAM)-1, B7.1, B7.2, CD40 and CD40 ligand (CD40L) on monocytes was examined. Prostaglandin E1 suppressed B7.1 and CD40 expression, but prostaglandin E2 did not effect on any type of adhesion molecule expression. Both prostaglandins inhibited tumor necrosis factor (TNF)-alpha production and T-cell proliferation of lipopolysaccharide-treated human peripheral blood mononuclear cells (PBMC). Among prostaglandin E1 receptors (IP/EP1/EP2/EP3/EP4) agonists, ONO-1301, a prostanoid IP-receptor agonist, prevented B7.1 and CD40 expression. ONO-AE1-259-01 a prostanoid EP2-receptor agonist, ONO-AE1-329, a prostanoid EP4-receptor agonist, and ONO-1301 inhibited TNF-alpha production and T-cell proliferation. Moreover, anti-B7.1 and anti-CD40 Abs prevented lipopolysaccharide-induced TNF-alpha production and T-cell proliferation. Therefore, the effect of prostaglandin E1 on TNF-alpha production and T-cell proliferation might depend on the inhibition of B7.1 and CD40 expression, but that of prostaglandin E2 might be independent of adhesion molecules expression. In conclusion, the mechanism responsible for the effect of prostaglandin E1 on lipopolysaccharide-induced responses is distinct from that of prostaglandin E2.
研究了前列腺素E1和E2对1 ng/ml脂多糖诱导的单核细胞细胞间黏附分子（ICAM）-1、B7.1、B7.2、CD40和CD40配体（CD40L）表达的影响。前列腺素E1抑制B7.1和CD40表达，但前列腺素E2对任何类型的黏附分子表达均无影响。两种前列腺素均抑制脂多糖处理的人外周血单个核细胞（PBMC）的肿瘤坏死因子（TNF）-α产生和T细胞增殖。在前列腺素E1受体（IP/EP1/EP2/EP3/EP4）激动剂中，前列环素IP受体激动剂ONO-1301可阻止B7.1和CD40表达。前列环素EP2受体激动剂ONO-AE1-259-01、前列环素EP4受体激动剂ONO-AE1-329和ONO-1301抑制TNF-α产生和T细胞增殖。此外，抗B7.1和抗CD40抗体可阻止脂多糖诱导的TNF-α产生和T细胞增殖。因此，前列腺素E1对TNF-α产生和T细胞增殖的影响可能取决于对B7.1和CD40表达的抑制，但前列腺素E2的影响可能与黏附分子表达无关。总之，前列腺素E1对脂多糖诱导反应的作用机制与前列腺素E2不同。
