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Cell Biochemistry and Biophysics

, Volume 59, Issue 2, pp 89–97 | Cite as

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

  • Thais Martins de Lima-SalgadoEmail author
  • Tatiana C. Alba-Loureiro
  • Caroline S. do Nascimento
  • Maria T. Nunes
  • Rui Curi
Original Research

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.

Keywords

Saturated fatty acid TNF-α Gene expression Poly(A) tail Transcription factors 

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

Notes

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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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Thais Martins de Lima-Salgado
    • 1
    Email author
  • Tatiana C. Alba-Loureiro
    • 2
  • Caroline S. do Nascimento
    • 3
  • Maria T. Nunes
    • 3
  • Rui Curi
    • 2
  1. 1.Laboratory of Clinical Emergency (LIM51), Emergency Medicine Department, Medical SchoolUniversity of São PauloSão PauloBrazil
  2. 2.Department of Physiology and Biophysics, Institute of Biomedical SciencesUniversity of São PauloSão PauloBrazil
  3. 3.Department of Physiology and Biophysics, Institute of Biomedical SciencesUniversity of São PauloSão PauloBrazil

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