Molecular Mechanisms by Which Saturated Fatty Acids Modulate TNF-alpha Expression in Mouse Macrophage Lineage

Autor(es)

de Lima-Salgado, Thais Martins ^[1] ; Alba-Loureiro, Tatiana C. ^[2] ; do Nascimento, Caroline S. ^[2] ; Nunes, Maria T. ^[2] ; Curi, Rui ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med, Dept Emergency Med, Lab Clin Emergency LIM51, BR-01246903 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Cell Biochemistry and Biophysics; v. 59, n. 2, p. 89-97, MAR 2011.
• Citações Web of Science: 24

Resumo

Many macrophage functions are modulated by fatty acids (FAs), including cytokine release, such as tumor necrosis factor-alpha (TNF-alpha). TNF-alpha is of great interest due to its role in the inflammation process observed in several diseases such as rheumatoid arthritis, atherosclerosis, and obesity. However, the mechanisms by which FA effects occur have not been completely elucidated yet. In this study, we used a mouse monocyte lineage (J774 cells) to evaluate the effect of 50 and 100 mu M of saturated (palmitic and stearic acids), monounsaturated (oleic acid) and polyunsaturated (linoleic acid) FAs on TNF-alpha production. Alterations in gene expression, poly(A) tail length and activation of transcription factors were evaluated. Oleic and linoleic acids, usually known as neutral or pro-inflammatory FA, inhibited LPS-induced TNF-alpha secretion by the cells. Saturated FAs were potent inducers of TNF-alpha expression and secretion under basal and inflammatory conditions (in the presence of LPS). Although the effect of the saturated FA was similar, the mechanism involved in each case seem to be distinct, as palmitic acid increased EGR-1 and CREB binding activity and stearic acid increased mRNA poly(A) tail. These results may contribute to the understanding of the molecular mechanisms by which saturated FAs modulate the inflammatory response and may lead to design of associations of dietary and pharmacological strategies to counteract the pathological effects of TNF-alpha. (AU)

• Processo FAPESP: 06/02709-3 - Efeitos de ácidos graxos sobre a produção e sinalização de TNF alfa em macrófagos
• Beneficiário: Thais Martins de Lima Salgado
• Linha de fomento: Bolsas no Brasil - Pós-Doutorado