IL-17 regulates gene expression and protein synthesis of the complement system, C3 and factor B, in skin fibroblasts

Yitzhak Katz, O. Nadiv, M. J. Rapoport, M. Loos

Research output: Contribution to journalArticlepeer-review

Abstract

Human IL-17 is a cytokine secreted by CD4+-activated memory T cells with the profile of effects of a Th1 cytokine. The effects of IL-17 on many cellular constituents of joints suggest that it may participate in inflammatory joint diseases. Proteins of the complement system are known to be regulated by pro- and anti-inflammatory cytokines. The purpose of this work was to study the effect of IL-17 alone and combined with tumour necrosis factor (TNF) on the expression and synthesis of factor B and C3. Fibroblasts were stimulated with the relevant cytokine or cytokines, pulse labelled with 35S-methionine, and the newly synthesized proteins were immunoprecipitated and subjected to SDS-PAGE. Gene expression was determined by Northern blot analysis. IL-17 10 ng/ml induced increases in gene expression and protein synthesis of C3, 2.25 ± 0-26- and 2.7 ≠ 0.7-fold, respectively, with concomitant non-significant effects on factor B, 1.5 ± 0.45- and 2.2 ± 1.2- fold, respectively. When both IL-17 and TNF were present simultaneously, the synthesis of factor B increased by 85% more than the expected additive effects of these cytokines separately, while for C3 the effect of both cytokines was 19% lower than the expected additive effect (observed/expected = 0.81). IL-4 reduced the synergistic effect by 50%. We conclude that IL-17 has a regulatory role on C3 expression and synthesis and an amplifying effect on TNF-induced factor B synthesis. Taken together with the evidence that TNF is a major cytokine involved in the inflammation of rheumatoid arthritis, it suggests that IL-17 has a proinflammatory role in the inflammation process of joints. The distinct effects of IL-4, IL-17 and TNF on the synthesis of factor B in fibroblasts suggest that factor B and the alternative pathway of the complement system may play an important role in joint inflammation.

Original languageEnglish
Pages (from-to)22-29
Number of pages8
JournalClinical and Experimental Immunology
Volume120
Issue number1
DOIs
StatePublished - 2000

Keywords

  • Complement
  • Fibroblasts
  • IL-17
  • Tumour necrosis factor

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