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-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.
Footnotes
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Send reprint requests to: David M. Essayan, M.D., The Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Room 1A12, Baltimore, MD 21224. E-mail:dessayan{at}jhmi.edu
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1 This work was supported by grants AI34002 and AI07290 from the National Institute of Allergy and Infectious Diseases, National Institutes of Health.
- Abbreviations:
- ECM
- extracellular matrix
- KF
- keloid fibroblast
- MMP
- matrix metalloproteinase
- NF
- normal fibroblast
- Col1α
- procollagen 1α1
- Col3α
- procollagen 3α1
- OH-Pro
- hydroxyproline
- IL
- interleukin
- TGF
- transforming growth factor
- PCR
- polymerase chain reaction
- RT
- reverse transcription
- TIMP
- tissue inhibitor of metalloproteinase
- Received July 16, 1999.
- Accepted November 8, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
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