PT  - JOURNAL ARTICLE
AU  - Alfonso Oriente
AU  - Neal S. Fedarko
AU  - Sarah E. Pacocha
AU  - Shau-Ku Huang
AU  - Lawrence M. Lichtenstein
AU  - David M. Essayan
TI  - Interleukin-13 Modulates Collagen Homeostasis in Human Skin and Keloid Fibroblasts
DP  - 2000 Mar 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 988--994
VI  - 292
IP  - 3
4099  - http://jpet.aspetjournals.org/content/292/3/988.short
4100  - http://jpet.aspetjournals.org/content/292/3/988.full
SO  - J Pharmacol Exp Ther2000 Mar 01; 292
AB  - 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-β1transiently 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. The American Society for Pharmacology and Experimental Therapeutics