title: Nitric oxide induces SOCS-1 expression in human monocytes in a TNF-alpha-dependent manner.
abstract: In contrast to the thoroughly characterized mechanisms of positive regulation within cytokine signaling pathways, our knowledge of negative feedback loops is comparatively sparse. We and others have previously reported that IRAK-M down-regulates inflammatory responses to multiple stimuli. In particular, we could show that the nitric oxide (NO) donor, GSNO, induces IRAK-M overexpression in human monocytes. Here we study the expression of another important negative regulator of cytokine signaling, SOCS-1, in human monocytes exposed to GSNO. The NO donor induced significant levels of SOCS-1 mRNA and protein, 6 h and 16 h after stimulation, respectively. Monocytes stimulated with GSNO for longer periods (24 h and 48 h) failed to express IL-6 and IP-10 upon LPS challenge. In addition, and in line with previous reports of NO-mediated induction of TNF-alpha, we have found that exposure to this cytokine induces SOCS-1 mRNA in human monocytes. A blocking antibody against TNF-alpha impaired SOCS-1 expression upon GSNO treatment and re-instated IL-6 and IP-10 mRNA levels after LPS challenge in cultures pretreated with the NO donor. We conclude that NO stimulates SOCS-1 overexpression in a pathway at least partially regulated by TNF-alpha.
authors.affiliation: Research Unit, La Paz Hospital, Madrid, Spain.
authors.forename: M Carmen
authors.initials: MC
authors.lastname: González-León
authors.forename: Alessandra
authors.initials: A
authors.lastname: Soares-Schanoski
authors.forename: Carlos
authors.initials: C
authors.lastname: del Fresno
authors.forename: Agata
authors.initials: A
authors.lastname: Cimadevila
authors.forename: Vanesa
authors.initials: V
authors.lastname: Goméz-Piña
authors.forename: Elena
authors.initials: E
authors.lastname: Mendoza-Barberá
authors.forename: Felipe
authors.initials: F
authors.lastname: García
authors.forename: Elvira
authors.initials: E
authors.lastname: Marín
authors.forename: Francisco
authors.initials: F
authors.lastname: Arnalich
authors.forename: Pablo
authors.initials: P
authors.lastname: Fuentes-Prior
authors.forename: Eduardo
authors.initials: E
authors.lastname: López-Collazo
mesh_terms: D002478:Cells, Cultured; D006801:Humans; D007700:Kinetics; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D009569:Nitric Oxide / Q000494:pharmacology*; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide