Synergy Between CD40 Ligation and IL-4 on Fibroblast Proliferation Involves IL-4 Receptor Signaling
| Autor: | Heqiao Dai, Sergei P. Atamas, Susan G. Wilt, Barbara White, Irina G. Luzina |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
CD40 Ligand
Immunology Biology Cell Line medicine Humans Immunology and Allergy Fibroblast Autocrine signalling Janus kinase 1 Fibroblast growth factor receptor 2 Drug Synergism Fibroblast growth factor receptor 4 Fibroblasts Protein-Tyrosine Kinases Fibroblast growth factor receptor 3 Molecular biology Receptors Interleukin-4 Autocrine Communication medicine.anatomical_structure Fibroblast growth factor receptor Cytokines Interleukin-4 Signal transduction Cell Division Signal Transduction |
| Zdroj: | The Journal of Immunology. 168:1139-1145 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.168.3.1139 |
| Popis: | Fibrosis can be an undesired consequence of activated cellular immune responses. The purpose of this work was to determine whether CD40 ligation and the pro-fibrotic cytokine IL-4 interact in regulating fibroblast proliferation and collagen production, and, if so, the mechanisms used. This study found that the combination of IL-4 and ligation of CD40 on the fibroblast cell surface had synergistic effects in stimulating fibroblast proliferation. In contrast, CD40 ligation negated the inhibitory effects of IFN-γ on fibroblast proliferation. Western blotting analyses of fibroblast crude lysates revealed that a potential mechanism of the synergy between CD40 ligation and IL-4 was the phosphorylation of proteins at 130 kDa and, to a lesser degree, at 95, 85, and 75 kDa. Immunoprecipitation-Western blotting experiments showed that phosphorylation levels of IL-4Rα, Janus kinase 1, insulin receptor substrate 1, and insulin receptor substrate 2, factors with molecular mass close to the observed 130 kDa major phosphorylation band, increased in response to the combined CD40 ligation and IL-4 action. In contrast, there was no evidence that synergy was mediated by an increased expression of IL-4Rα chain, CD40, or the autocrine profibrotic cytokines IL-6 and TGF-β. These findings suggest that CD40-CD40 ligand contacts between fibroblasts and cells secreting IL-4 may promote the profibrotic effects of IL-4 by affecting signal transduction and reducing the anti-fibrotic effects of IFN-γ. |
| Databáze: | OpenAIRE |
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