title: Curcumin abrogates LPS-induced pro-inflammatory cytokines in RAW 264.7 macrophages. Evidence for novel mechanisms involving SOCS-1, -3 and p38 MAPK.
abstract: Curcumin is the active compound in the extract of Curcuma longa rhizomes with anti-inflammatory properties mediated by inhibition of intracellular signalling. SOCS and MAPKinases are involved in the signalling events controlling the expression of IL-6, TNF-α and PGE2, which have important roles on chronic inflammatory diseases. The aim was to assess if these pathways are involved in curcumin-mediated effects on LPS-induced expression of these cytokines in macrophages. RAW 264.7 murine macrophages were stimulated with Escherichia coli LPS in the presence and absence of non-cytotoxic concentrations of curcumin. Curcumin potently inhibited LPS-induced expression of IL-6, TNF-α and COX-2 mRNA and prevented LPS-induced inhibition of SOCS-1 and -3 expression and the inhibition of the activation of p38 MAPKinase by modulation of its nuclear translocation. In conclusion, curcumin potently inhibits expression of LPS-induced inflammatory cytokines in macrophages via mechanisms that involve modulation of expression and activity of SOCS-1 and SOCS-3 and of p38 MAPK.
authors.affiliation: Department of Diagnosis and Surgery, Faculdade de Odontologia de Araraquara, Univ Estadual Paulista (UNESP), Araraquara, SP, Brazil.
authors.forename: Morgana Rodrigues
authors.initials: MR
authors.lastname: Guimarães
authors.forename: Fábio Renato Manzoli
authors.initials: FR
authors.lastname: Leite
authors.forename: Luís Carlos
authors.initials: LC
authors.lastname: Spolidorio
authors.forename: Keith Lough
authors.initials: KL
authors.lastname: Kirkwood
authors.forename: Carlos
authors.initials: C
authors.lastname: Rossa
mesh_terms: D000818:Animals; D003474:Curcumin / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D007113:Immunity, Innate; D015850:Interleukin-6 / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D012333:RNA, Messenger / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology*
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014409:Tumor Necrosis Factor-alpha; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D048051:p38 Mitogen-Activated Protein Kinases; D003474:Curcumin
keywords: Cell signalling; Curcumin; Cytokines; Innate immunity; MAPK; NF-kB; SOCS