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