TNF activatesp38 MAPK to control Il-12/23p40 production in LPS-stimulated macrophages.

JERÉZ MB; MAYORDOMO AC; ARIAS JL,; JURI AYUB M; DI GENARO MS

Buenos Aires

Congreso; LXIII Reunión Anual de SAI en el marco del Primer Congreso Internacional conjunto (I Meeting LASID-SAI-FAIC) junto a LASID (IV Meeting LASID) y FAIC(FAIC-II),; 2015

Sociedad Argentina de Inmunlogia

Abstract: Background: Our previous studies demonstrated that TNFRp55 signaling controls the inflammatory response of LPS-stimulated macrophages. However, the molecular mechanisms involved in this effect remain uncertain. Mitogen-activated protein kinase (MAPK) cascade is a pathway triggered by TNFRp55. The aim was to investigate in peritoneal macrophages, the MAPK subtype cascade involved in the immunomodulatory role of TNF on IL-12/23p40 production.Methods: Peritoneal macrophages were obtained from C57BL/6 wild-type (WT) TNFRp55-/- and IL-10-/- mice 4 days after intraperitoneal inoculation of 4% thioglycolate broth. Adherent cells (7 x 105 cell/well) were stimulated with LPS (100ng/ml) in presence of p38 (SB203580), ERK (PD98059) or JNK (SP600125) MAPKs inhibitors. IL-12/23p40 level was determined in the supernatants by ELISA. The effects of the TNFRp55-specific stimulus (human TNF, 60ng/ml) or inhibitor (CAY10500, 0.1-1ug/ml) were also evaluated.Results: We observed that JNK and p38 inhibitors increased IL-12/23p40 levels in WT macrophages (p