Yucel-Lindberg T, Ahola H, Carlstedt-Duke J, Modéer T
Department of Pediatric Dentistry, Karolinska Institutet, Huddinge, Sweden. tulay@
Biochem Biophys Res Commun. 1999 Apr 13;257(2):528-32. doi: 10.1006/bbrc.1999.0523.
The purpose of the present study was to investigate the involvement of cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and tyrosine kinase on prostaglandin E2 (PGE2) production in human gingival fibroblasts stimulated by interleukin-1beta (IL-1beta) and/or epidermal growth factor (EGF). The cytokine IL-1beta and to a lesser extent EGF, enhanced COX-2 mRNA levels in gingival fibroblasts. Simultaneous treatment with EGF and IL-1beta resulted in enhanced COX-2 mRNA levels accompanied by a synergistic stimulation of PGE2 biosynthesis compared to the cells treated with IL-1beta or EGF alone. Neither IL-1beta EGF nor the combination of IL-1beta and EGF enhanced COX-1 mRNA levels in gingival fibroblasts. The tyrosine kinase inhibitors, Herbimycin A and PD 153035 hydrochloride, reduced COX-2 mRNA levels as well as PGE2 production induced by IL-1beta or the combination of IL-1beta and EGF whereas COX-1 mRNA levels were not affected. Furthermore, the COX-2 specific inhibitor, NS-398, abolished the PGE2 production induced by IL-1beta, EGF, or the combination. These results indicate that the synergy between IL-1beta and EGF on PGE2 production is due to an enhanced gene expression of COX-2 and that tyrosine kinase(s) are involved in the signal transduction of COX-2 in gingival fibroblasts.
本研究的目的是调查环氧合酶-1（COX-1）、环氧合酶-2（COX-2）和酪氨酸激酶在白细胞介素-1β（IL-1β）和/或表皮生长因子（EGF）刺激的人牙龈成纤维细胞中前列腺素E2（PGE2）产生过程中的作用。细胞因子IL-1β以及程度较轻的EGF可提高牙龈成纤维细胞中COX-2的mRNA水平。与单独用IL-1β或EGF处理的细胞相比，同时用EGF和IL-1β处理可使COX-2的mRNA水平升高，并伴随对PGE2生物合成的协同刺激。IL-1β、EGF以及IL-1β与EGF的组合均未提高牙龈成纤维细胞中COX-1的mRNA水平。酪氨酸激酶抑制剂赫曲霉素A和盐酸PD 153035可降低IL-1β或IL-1β与EGF组合诱导的COX-2 mRNA水平以及PGE2的产生，而COX-1 mRNA水平不受影响。此外，COX-2特异性抑制剂NS-398可消除IL-1β、EGF或其组合诱导的PGE2产生。这些结果表明，IL-1β与EGF在PGE²产生上的协同作用是由于COX-2基因表达增强，并且酪氨酸激酶参与了牙龈成纤维细胞中COX-2的信号转导。
