Novel functions of intracellular IL-1ra in human dermal fibroblasts: Implications in the pathogenesis of fibrosis

Siva Kanangat, Arnold Postlethwaite, Gloria C. Higgins, Karen Hasty

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Intracellular IL-1 receptor antagonist (icIL-1ra) is reportedly involved in functions independent of blocking IL-1 receptor signaling. Fibroblasts derived from the involved skin of patients with systemic sclerosis (SSc) are predominantly of the myofibroblast phenotype, with higher levels of icIL-1ra compared to normal skin fibroblasts. We examined the effect of overexpression of icIL-1ra on the phenotype and function of normal fibroblasts with respect to the expression of alpha smooth muscle actin (α-SMA), a specific marker for myofibroblasts, and plasminogen activator inhibitor (PAI), a protein involved in fibrogenesis and expressed at higher levels in myofibroblasts, and the production of collagenase (matrix metalloproteinase-1 (MMP-1)), the major enzyme involved in the degradation of native collagen in the skin. Normal human foreskin fibroblasts overexpressing icIL-1ra showed higher levels of α-SMA and PAI and had lower levels of collagenase and MMP-1 mRNA induced by inflammatory cytokines. By contrast, levels of mRNA for tissue inhibitor of metalloproteinase-1 in the transfected cells were not different from the control cells. Pretreatment of the ic-IL-1ra-transfected cells with antisense oligonucleotide directed against the mRNA of icIL-1ra restored MMP-1 expression induced by stimulation with IL-1β. Our data indicate novel functions for icIL-1ra, which might be relevant to the genesis of fibrotic diseases such as SSc.

Original languageEnglish (US)
Pages (from-to)756-765
Number of pages10
JournalJournal of Investigative Dermatology
Volume126
Issue number4
DOIs
StatePublished - Apr 1 2006

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Interleukin 1 Receptor Antagonist Protein
Interleukin-1 Receptors
Fibroblasts
Fibrosis
Skin
Matrix Metalloproteinase 1
Myofibroblasts
Plasminogen Inactivators
Systemic Scleroderma
Collagenases
Messenger RNA
Phenotype
Foreskin
Tissue Inhibitor of Metalloproteinase-1
Antisense Oligonucleotides
Interleukin-1
Smooth Muscle
Muscle
Actins
Collagen

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Novel functions of intracellular IL-1ra in human dermal fibroblasts : Implications in the pathogenesis of fibrosis. / Kanangat, Siva; Postlethwaite, Arnold; Higgins, Gloria C.; Hasty, Karen.

In: Journal of Investigative Dermatology, Vol. 126, No. 4, 01.04.2006, p. 756-765.

Research output: Contribution to journalArticle

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