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Published on: February 23, 2018
Induction of complement factor B activity in human fibroblasts by IL-6/IFN-beta 2 and IFN-gamma
I Barash1, Z Fishelson, M Revel
1Molecular Genetics and Virology Department, Weizmann Institute of Science, Rehovot, Israel.
Insights
Human skin fibroblasts produce complement Factor B when inflammation occurs. Interleukin-6 (IL-6) and Interferon-gamma (IFN-gamma) significantly boost this production, suggesting a role in inflammatory responses.
Area of Science:
- Immunology
- Cell Biology
- Inflammation Research
Background:
- Human skin fibroblasts synthesize and secrete complement Factor B, a key component of the complement alternative pathway.
- Inflammatory mediators like lipopolysaccharide and cytokines can stimulate Factor B production in fibroblasts.
Purpose of the Study:
- To investigate the role of Interleukin-6 (IL-6) and Interferon-gamma (IFN-gamma) in stimulating complement Factor B synthesis in human skin fibroblasts.
- To determine if these cytokines cooperate to enhance Factor B secretion and biological activity.
Main Methods:
- Fibroblast cell cultures were stimulated with recombinant IL-6/IFN-beta 2 and IFN-gamma.
- Factor B synthesis and secretion were measured.
- Biological activity of secreted Factor B was assessed using a hemolysis test.
- Cooperative effects of IL-6 and IFN-gamma on (2'-5') A synthetase induction were also examined.
Main Results:
- Recombinant IL-6/IFN-beta 2 alone stimulated Factor B synthesis.
- The addition of IFN-gamma significantly potentiated the effect of IL-6 on Factor B synthesis.
- Co-stimulation with IL-6 and IFN-gamma resulted in the secretion of biologically active Factor B.
- IL-6 and IFN-gamma also cooperated in inducing (2'-5') A synthetase.
Conclusions:
- IL-6 and IFN-gamma exhibit a cooperative effect in stimulating the synthesis and secretion of biologically active complement Factor B by human skin fibroblasts.
- This synergistic cytokine action may contribute to local inflammatory processes.
- The cooperation between IL-6 and IFN-gamma extends to the induction of (2'-5') A synthetase, a mediator of interferon action.
Abstract:
Human skin fibroblasts synthesize and secrete complement Factor B, a component of the complement alternative pathway, when stimulated by mediators of inflammation such as lipopolysaccharide and various cytokines. Recombinant IL-6/IFN-beta 2 (E. coli) stimulates Factor B synthesis in fibroblasts but the effect is strongly potentiated by the addition of IFN-gamma. When both cytokines are added, the skin fibroblasts secrete significant amounts of biologically active Factor B detectable in a hemolysis test. This cooperative effect of IL-6, which is made by most tissue cells and monocytes and of IFN-gamma which is made by T-lymphocytes may play a role in local inflammatory processes. IL-6 and IFN-gamma also cooperate in the induction of (2'-5') A synthetase, a mediator of IFN action.
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