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Interleukin-1 Enhances Type I Collagen-induced Activation of Matrix Metalloproteinase-2 in Odontogenic Keratocyst Fibroblasts

Second Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan;

*corresponding author, yasu{at}dent.kyushu-u.ac.jp

Interleukin-1 (IL-1) is strongly expressed in odontogenic keratocysts. In this study, we investigated the effects of IL-1 on the activation of matrix metalloproteinase-2 (MMP-2) in the fibroblasts isolated from odontogenic keratocysts. Odontogenic keratocyst fibroblasts secreted a latent form of MMP-2 (proMMP-2) spontaneously. Type I collagen induced the activation of the proMMP-2, and recombinant human IL-1 (rhIL-1) further enhanced the type I collagen-induced activation of proMMP-2 in a dose-dependent manner. The rhIL-1-induced activation of proMMP-2 was inhibited by anti-human IL-1 antibody. A reverse-transcription/polymerase chain-reaction (RT-PCR) and Western immunoblotting demonstrated that the expression of membrane-type 1 matrix metalloproteinase (MT1-MMP) mRNA and protein was increased in the fibroblasts when the cells were cultured on type I collagen, and the expression was further enhanced by rhIL-1. Thus, IL-1 may up-regulate proMMP-2 activation by increasing the expression of MT1-MMP in the fibroblasts isolated from odontogenic keratocysts synergistically with type I collagen.

KEY WORDS: interleukin-1a • type I collagen • matrix metalloproteinase-2 • membrane-type matrix metalloproteinases • odontogenic keratocyst

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