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

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Abstract

Many macrophage functions are modulated by fatty acids (FAs), including cytokine release, such as tumor necrosis factor-α (TNF-α). TNF-α 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 μM of saturated (palmitic and stearic acids), monounsaturated (oleic acid) and polyunsaturated (linoleic acid) FAs on TNF-α 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-α secretion by the cells. Saturated FAs were potent inducers of TNF-α 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-α.

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Abbreviations

FA:

Fatty acid

LPS:

Lipopolysaccharide

EGR-1:

Early growth response 1

CREB:

cAMP responsive element binding

NFκB:

Nuclear factor kappa B

AP:

Activator protein

C/EBPb:

Controlled amino acid therapy (CAAT)/enhancer binding protein

FCS:

Fetal calf serum

PA:

Palmitic acid

SA:

Stearic acid

OA:

Oleic acid

LA:

Linoleic acid

RT-PCR:

Reverse transcriptase-polymerase chain reaction

B2M:

β-2 microglobulin

MMLV:

Moloney murine leukemia virus

RACE:

Rapid amplification of cDNA ends

PAT:

Polyadenylation tail

EMSA:

Electrophoretic mobility shift assay

PNK:

Polynucleotide kinase

TLR:

Toll-like receptor

IL:

Interleukin

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Acknowledgments

The authors are grateful to the technical assistance of G. de Souza, J. R. Mendonça, and E. P. Portioli. This research is supported by FAPESP, CNPq, and CAPES.

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Authors and Affiliations

  1. Laboratory of Clinical Emergency (LIM51), Emergency Medicine Department, Medical School, University of São Paulo, Av. Dr. Arnaldo 455, Room 3189, São Paulo, SP, 01246-903, Brazil

    Thais Martins de Lima-Salgado

  2. Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 1524, Room 105, São Paulo, SP, 05508-900, Brazil

    Tatiana C. Alba-Loureiro & Rui Curi

  3. Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 1524, Room 131, São Paulo, SP, 05508-900, Brazil

    Caroline S. do Nascimento & Maria T. Nunes

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  1. Thais Martins de Lima-Salgado
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  2. Tatiana C. Alba-Loureiro
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  3. Caroline S. do Nascimento
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Correspondence to Thais Martins de Lima-Salgado.

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This study was supported by the FAPESP-2006/02709-3.

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de Lima-Salgado, T.M., Alba-Loureiro, T.C., do Nascimento, C.S. et al. Molecular Mechanisms by Which Saturated Fatty Acids Modulate TNF-α Expression in Mouse Macrophage Lineage. Cell Biochem Biophys 59, 89–97 (2011). https://doi.org/10.1007/s12013-010-9117-9

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  • DOI: https://doi.org/10.1007/s12013-010-9117-9

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