Papers of The 1st Japan Scar Workshop

3. Functional Analysis of The IL-6 Signaling Pathway in Keloid Pathogenesis

Tosa, Ghazizadeh M2, Murakami M1, Kawanami O2, Hyakusoku H3.
1: Department of Plastic and Reconstructive Surgery, Nippon Medical School2nd Hosupital, Kanagawa, Japan
2: Department of Molecular Pathology, Institute of Gerontology, Graduate School of Medicine, Nippon Medical School, Kanagawa, Japan
3: Department of Plastic and Reconstructive Surgery, Nippon Medical School Hospital, Tokyo, Japan


A keloid is a dermal fibroproliferative lesion of unknown etiology. Previously, by global gene expression analysis of keloid fibroblasts (KFs), we determined that the IL-6 signaling pathway was implicated in keloid pathogenesis. In studying the functional role of the signaling of interleukin-6 (IL-6) in the formation of keloids, we found that the secretion of IL-6 was significantly higher in keloid dermal fibroblasts (KFs) than in those that were normal (NFs). The addition of IL-6 peptide to NF culture or inhibition of IL-6 or its receptor, IL-6R alpha, by their corresponding antibodies in KF culture revealed a dose-dependent increase or decrease in collagen type I alpha 2 and fibronectin mRNAs, respectively. Induction of IL-6 and stimulation in NF culture or inhibition of IL-6 or IL-6R alpha in KF culture demonstrated, respectively, a dose-dependent increase or decrease in the synthesis of procollagen I. The mRNA and protein expressions of gp130 and several downstream targets in IL-6 signaling were upregulated in KFs versus NFs. Our results indicate that IL-6 signaling may play an integral role in the pathogenesis of keloids.
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