Interleukin-13 modulates collagen homeostasis in human skin and keloid fibroblasts

Alfonso Oriente, Neal S. Fedarko, Sarah E. Pacocha, Shau Ku Huang, Lawrence M. Lichtenstein, David M. Essayan

Research output: Contribution to journalArticle

172 Citations (Scopus)

Abstract

Interleukin (IL)-13 has been implicated in the pathogenesis of various diseases characterized by fibrosis. We describe the effects of IL-13 on collagen homeostasis from normal (NF) and keloid (KF) fibroblasts and compare these effects with those of IL-4 and transforming growth factor (TGF)-β1. Total collagen generation was up-regulated in NF after 48 h of stimulation by IL-13; in KF, IL-13 stimulated a more rapid collagen response. The kinetics and magnitude of collagen generation induced by IL-13 were equivalent to those induced by similar concentrations of IL-4 and TGF-β1. Collagen type I production paralleled total collagen generation from both NF and KF; however, IL-4-induced collagen type I and total collagen production from KF was more transient than that induced by either IL-13 or TGF-β1. Procollagen 1α1 gene expression was induced in KF by stimulation with IL-13 for 24 h. Moreover, IL-13 was unique among these three cytokines in its ability to induce gene expression for procollagen 3α1. Finally, IL-13 inhibited IL-1β- induced matrix metalloproteinase (MMP)-1 and MMP-3 production and enhanced tissue inhibitor of metalloproteinase (TIMP)-1 generation from NF; although similar effects were observed with IL-4 TGF-β1 transiently enhanced MMP-1 and MMP-3 generation without effecting TIMP-1. In KF, IL-13 and IL-4 inhibited MMP-3, whereas TGF-β1 enhanced MMP-3; TIMP-1 was unaffected by any of the three cytokines. These data demonstrate both the profibrotic effects of IL-13 on collagen homeostasis and the potential differential regulation of collagen homeostasis in fibroblast subtypes by IL-13.

Original languageEnglish
Pages (from-to)988-994
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume292
Issue number3
Publication statusPublished - Mar 1 2000
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Pharmacology

Cite this

Oriente, A., Fedarko, N. S., Pacocha, S. E., Huang, S. K., Lichtenstein, L. M., & Essayan, D. M. (2000). Interleukin-13 modulates collagen homeostasis in human skin and keloid fibroblasts. Journal of Pharmacology and Experimental Therapeutics, 292(3), 988-994.