Keelan J A, Sato T A, Mitchell M D
Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine and Health Science, University of Auckland School of Medicine, New Zealand.
Am J Reprod Immunol. 1998 Nov;40(5):332-8. doi: 10.1111/j.1600-0897.1998.tb00062.x.
In hematopoietic cells, interleukin (IL)-13 shares many actions with IL-4. The effects of IL-13 in gestational tissues have yet to be reported, however. We compared the effects of IL-4 and IL-13 on the production of cytokines and prostaglandin E2 (PGE2) in epithelial amnion-derived WISH cells.
WISH cells were treated with IL-4 or IL-13 (0.08-10 ng/ml) with/without cotreatment with IL-1 beta (0.2 ng/ml), tumor necrosis factor-alpha (10 ng/ml) or epidermal growth factor (5 ng/ml). The production of IL-6, IL-8, and PGE2 was measured by immunoassay after 16 hr.
Both IL-4 and IL-13 inhibited PGE2 production with indistinguishable concentration-response curves, under basal or stimulated conditions. The maximal inhibition of IL-1 beta-stimulated PGE2 production (to 28% +/- 10% of control) was seen at 10 ng/ml of IL-4 or IL-13. Basal IL-6 production was stimulated approximately twofold by IL-4 and IL-13, whereas IL-4 and IL-13 both inhibited cytokine-stimulated (but not basal) IL-8 production by approximately 50%. In the presence of 1 ng/ml of IL-4, IL-13 was unable to further inhibit PGE2 production.
The inhibition of PGE2 and IL-8 production by IL-4 in WISH cells is mimicked by IL-13. Both cytokines, probably through binding to a common receptor complex, may share a role in suppressing inflammatory reactions within intrauterine tissues.
在造血细胞中,白细胞介素(IL)-13与IL-4具有许多共同作用。然而,IL-13在妊娠组织中的作用尚未见报道。我们比较了IL-4和IL-13对羊膜上皮来源的WISH细胞中细胞因子和前列腺素E2(PGE2)产生的影响。
用IL-4或IL-13(0.08 - 10 ng/ml)处理WISH细胞,同时或不同时用IL-1β(0.2 ng/ml)、肿瘤坏死因子-α(10 ng/ml)或表皮生长因子(5 ng/ml)共处理。16小时后通过免疫测定法检测IL-6、IL-8和PGE2的产生。
在基础或刺激条件下,IL-4和IL-13均抑制PGE2的产生,其浓度 - 反应曲线难以区分。在10 ng/ml的IL-4或IL-13作用下,IL-1β刺激的PGE2产生受到最大抑制(降至对照的28%±10%)。基础IL-6的产生受到IL-4和IL-13的刺激,增加约两倍,而IL-4和IL-13均将细胞因子刺激(而非基础)的IL-8产生抑制约50%。在存在1 ng/ml IL-4的情况下,IL-13无法进一步抑制PGE2的产生。
IL-13模拟了IL-4对WISH细胞中PGE2和IL-8产生的抑制作用。这两种细胞因子可能通过与共同的受体复合物结合,在抑制子宫内组织的炎症反应中发挥共同作用。