SOCS3 Modulates Interleukin-6R Signaling Preference in Dermal Fibroblasts
Copyright policy )SOCS3 Modulates Interleukin-6R Signaling Preference in Dermal Fibroblasts
This study aims to investigate the mechanisms in the apparent preference for mitogen-activated protein kinase /ERK signaling through interleukin (IL)-6R in dermal fibroblasts.Dermal fibroblasts isolated from IL-6KO mice were pretreated with specific ERK or STAT3 chemical inhibitors or SOCS3 specific siRNA and treated with rmIL-6. Phosphorylation was monitored via enzyme-linked immunosorbent assay or immunohistology. SOCS3 interaction with p120Ras-Gap was examined by co-immunoprecipitation and Western blot. Expression of MMP2 mRNA was assessed via real-time quantitative polymerase chain reaction.A dose response phosphorylation of ERK1/2 occurred while no STAT3 activation (p-Tyr705) was induced after IL-6 treatment, despite an increase in Ser727 phosphorylation. Inhibition of STAT3 in fibroblasts potentiated IL-6R induced ERK phosphorylation and vice versa. Phosphorylated SOCS3 and p120 RasGAP co-immunoprecipitated in response to IL-6 treatment. SOCS3 siRNA knockdown allowed STAT3 phosphorylation after rmIL-6 treatment. Chemical inhibition of IL-6R signaling altered the IL-6 modulated mRNA expression of MMP-2.SOCS3 interaction with p120 Ras-Gap plays a role in determining the preference for IL-6R signaling through ERK in dermal fibroblasts. This study provides insight into the pleiotropic nature of IL-6 and the selective signaling mechanism elicited by the IL-6R system in dermal fibroblasts. It may further indicate a method for manipulation of IL-6R function.
- University of Oklahoma Health Sciences Center United States
- University of Oklahoma United States
Mice, Knockout, STAT3 Transcription Factor, Interleukin-6, Suppressor of Cytokine Signaling Proteins, p120 GTPase Activating Protein, Dermis, Fibroblasts, Receptors, Interleukin-6, Mice, Gene Expression Regulation, Suppressor of Cytokine Signaling 3 Protein, Animals, Matrix Metalloproteinase 2, Phosphorylation, RNA, Small Interfering, Extracellular Signal-Regulated MAP Kinases, Cells, Cultured, Signal Transduction
Mice, Knockout, STAT3 Transcription Factor, Interleukin-6, Suppressor of Cytokine Signaling Proteins, p120 GTPase Activating Protein, Dermis, Fibroblasts, Receptors, Interleukin-6, Mice, Gene Expression Regulation, Suppressor of Cytokine Signaling 3 Protein, Animals, Matrix Metalloproteinase 2, Phosphorylation, RNA, Small Interfering, Extracellular Signal-Regulated MAP Kinases, Cells, Cultured, Signal Transduction
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