IL-10 Inhibits the NF-kB and ERK/MAPK-Mediated Production of Pro-Inflammatory Mediators by UpRegulation of SOCS-3 in Trypanosoma cruzi-Infected Cardiomyocytes

Trypanosoma cruzi (T. cruzi) infection produces an intense inflammatory response which is critical for the control of the evolution of Chagas´ disease. Interleukin (IL)-10 is one of the most important anti-inflammatory cytokines identified as modulator of the inflammatory reaction. This work shows that exogenous addition of IL-10 inhibited ERK1/2 and NF-κB activation and reduced inducible nitric oxide synthase (NOS2), metalloprotease (MMP) -9 and MMP-2 expression and activities, as well as tumour necrosis factor (TNF)-α and interleukin (IL)-6 expression, in T. cruzi-infected cardiomyocytes. We found that T. cruzi and IL-10 promote STAT3 phosphorylation and up-regulate the expression of suppressor of cytokine signalling (SOCS)-3 thereby preventing NF-κB nuclear translocation and ERK1/2 phosphorylation. Specific knockdown of SOCS-3 by small interfering RNA (siRNA) impeded the IL-10-mediated inhibition of NF-κB and ERK1/2 activation. As a result, the levels of studied pro-inflammatory mediators were restored in infected cardiomyocytes. Our study reports the first evidence that T. cruzi up- regulates SOCS-3 expression and highlights the relevance of IL-10 in the modulation of pro-inflammatory response of cardiomyocytes in Chagas´ disease. ; Fil: Hovsepian, Eugenia. Consejo Nacional de Invest.cientif.y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones En Microbiologia y Parasitologia Medica; ; Fil: Penas, Federico Nicolás. Consejo Nacional de Invest.cientif.y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones En Microbiologia y Parasitologia Medica; ; Fil: Siffo, Sofía. Consejo Nacional de Invest.cientif.y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones En Microbiologia y Parasitologia Medica; ; Fil: Mirkin Gerardo A. INSTITUTO DE INVESTIGACIONES EN MICROBIOLOGIA Y PARASITOLOGIA MEDICA; ; Fil: Goren, Nora Beatriz. Consejo Nacional de Invest.cientif.y Tecnicas. Oficina de Coordinacion Administrativa Houssay. ...