环氧化酶-2抑制剂可降低白细胞介素-1β刺激人牙龈成纤维细胞产生前列腺素E2和白细胞介素-6的水平。

Cyclooxygenase-2 inhibitors decrease interleukin-1beta-stimulated prostaglandin E2 and IL-6 production by human gingival fibroblasts.

作者信息

Tipton David A, Flynn Jon C, Stein Sidney H, Dabbous Mustafa Kh

机构信息

Department of Periodontology, The University of Tennessee Health Science Center, College of Dentistry, Memphis, TN 38163, USA.

出版信息

J Periodontol. 2003 Dec;74(12):1754-63. doi: 10.1902/jop.2003.74.12.1754.

DOI:10.1902/jop.2003.74.12.1754

PMID:14974816

Abstract

BACKGROUND

Previous work showed that normal and aggressive periodontitis (AgP) gingival fibroblasts produce the bone-resorbing cytokine IL-6. PGE2 is important in regulating IL-6 production. Non-steroidal anti-inflammatory drugs inhibit PG synthesis via COX-1 and/or COX-2 isoenzymes and may inhibit periodontal destruction. COX-2 is induced after cellular activation (i.e., by inflammatory cytokines such as IL-1beta). Little is known about IL-1beta-stimulated AgP fibroblast IL-6 and PGE2 production and their regulation by COX inhibitors. The objective of this study was to determine the effects of COX-2 inhibitors on amounts of PGE2 and IL-6 made by IL-1beta-stimulated gingival fibroblasts.

METHODS

Gingival fibroblasts (2.5 x 10(4)) from healthy or severe periodontitis patients were cultured in serum-free medium, with or without IL-1beta (10(-11)M) for 24 hours, with or without the COX-1/2 inhibitor indomethacin or the selective COX-2 inhibitors NS-398, celecoxib, or rofecoxib. PGE2 and IL-6 in culture supernatants were determined by specific enzyme-linked immunosorbent assay (ELISA)s.

RESULTS

All of the COX inhibitors caused dose-dependent decreases in IL-1beta-stimulated PGE2, to a maximum of > 90% in all cell lines (P < or = 0.0001). The selective COX-2 inhibitors, but not indomethacin, caused partial (generally up to approximately 60%), dose-dependent decreases in IL-1beta-stimulated IL-6 in all cell lines (P < or = 0.003). When exogenous PGE2 was added concurrently with COX-2 inhibitors before addition of IL-1beta, IL-6 production returned to levels at or approaching that produced by cells exposed only to IL-1beta (P < or = 0.04).

CONCLUSION

The results suggest that COX-2 inhibition may be useful in helping to control fibroblast production of IL-6 in patients with severe periodontitis.

摘要

背景

先前的研究表明，正常和侵袭性牙周炎（AgP）的牙龈成纤维细胞可产生骨吸收细胞因子白细胞介素-6（IL-6）。前列腺素E2（PGE2）在调节IL-6的产生中起重要作用。非甾体类抗炎药通过环氧合酶-1（COX-1）和/或环氧合酶-2（COX-2）同工酶抑制前列腺素合成，可能抑制牙周组织破坏。COX-2在细胞活化后（即由白细胞介素-1β等炎性细胞因子）被诱导产生。关于白细胞介素-1β刺激的侵袭性牙周炎成纤维细胞中IL-6和PGE2的产生及其受COX抑制剂的调控知之甚少。本研究的目的是确定COX-2抑制剂对白细胞介素-1β刺激的牙龈成纤维细胞产生PGE2和IL-6量的影响。

方法

将来自健康或重度牙周炎患者的牙龈成纤维细胞（2.5×10⁴）在无血清培养基中培养，添加或不添加白细胞介素-1β（10⁻¹¹M）培养24小时，添加或不添加COX-1/2抑制剂吲哚美辛或选择性COX-2抑制剂NS-398、塞来昔布或罗非昔布。通过特异性酶联免疫吸附测定（ELISA）法测定培养上清液中的PGE2和IL-6。

结果

所有COX抑制剂均导致白细胞介素-1β刺激的PGE2呈剂量依赖性降低，在所有细胞系中最大降低幅度>90%（P≤0.0001）。选择性COX-2抑制剂而非吲哚美辛使所有细胞系中白细胞介素-1β刺激的IL-6呈部分性（一般高达约60%）剂量依赖性降低（P≤0.003）。在添加白细胞介素-1β之前，当外源性PGE2与COX-2抑制剂同时添加时，IL-6的产生恢复到仅暴露于白细胞介素-1β的细胞所产生的水平或接近该水平（P≤0.04）。