环孢素A在体外上调肿瘤坏死因子α刺激的人牙龈成纤维细胞中前列腺素E2的产生。

Cyclosporin A upregulates prostaglandin E2 production in human gingival fibroblasts challenged with tumor necrosis factor alpha in vitro.

作者信息

Wondimu B, Modéer T

机构信息

Department of Pediatric Dentistry, Faculty of Odontology, Karolinska Institute, Huddinge, Sweden.

出版信息

J Oral Pathol Med. 1997 Jan;26(1):11-6. doi: 10.1111/j.1600-0714.1997.tb00003.x.

DOI:10.1111/j.1600-0714.1997.tb00003.x

PMID:9021546

Abstract

The effect of cyclosporin A (CsA) on prostaglandin E2 (PGE2) production in human gingival fibroblasts challenged with tumor necrosis factor alpha (TNF-alpha) was studied. TNF-alpha (1-100 ng/ml) dose-dependently stimulated PGE2 formation in 24 h cultures. CsA (1-100 ng/ml) did not induce PGE2 formation itself but potentiated TNF-alpha induced PGE2 formation in gingival fibroblasts in a manner dependent on the concentrations of both CsA and TNF-alpha. TNF-alpha (10 ng/ml) stimulated the release of [3H]-arachidonic acid (AA) from prelabelled fibroblasts that was potentiated by CsA (100 ng/ml). Addition of exogenous unlabelled AA (5-20 microM/ml) to the cells resulted in enhanced PGE2 formation that was not potentiated by CsA (100 ng/ml). Furthermore, CsA (100 ng/ml) did not further increase the level of cyclooxygenase-2 mRNA induced by TNF-alpha (10 ng/ml), although PGE2 formation was enhanced. The results indicate that CsA and TNF-alpha act in concert on PGE2 formation in gingival fibroblasts, which may be of importance in the pathogenesis of gingival overgrowth induced by the drug.

摘要

研究了环孢素A（CsA）对用肿瘤坏死因子α（TNF-α）刺激的人牙龈成纤维细胞中前列腺素E2（PGE2）产生的影响。TNF-α（1-100 ng/ml）在24小时培养中剂量依赖性地刺激PGE2形成。CsA（1-100 ng/ml）本身不诱导PGE2形成，但以依赖于CsA和TNF-α浓度的方式增强TNF-α诱导的牙龈成纤维细胞中PGE2的形成。TNF-α（10 ng/ml）刺激预先标记的成纤维细胞释放[3H]-花生四烯酸（AA），这被CsA（100 ng/ml）增强。向细胞中添加外源性未标记的AA（5-20 microM/ml）导致PGE2形成增强，但未被CsA（100 ng/ml）增强。此外，尽管PGE2形成增强，但CsA（100 ng/ml）并未进一步增加由TNF-α（10 ng/ml）诱导的环氧合酶-2 mRNA水平。结果表明，CsA和TNF-α协同作用于牙龈成纤维细胞中PGE2的形成，这可能在该药物诱导的牙龈过度生长的发病机制中具有重要意义。