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Protein tyrosine phosphatase 1B (PTP1B) modulates palmitate-induced cytokine production in macrophage cells

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Abstract

Objective

The aim of the study was to investigate the effect of PTP1B modulation on palmitate-induced cytokine production in macrophages.

Methods

Lentiviruses carrying PTP1B-shRNA or cDNA at different multiplicities of infection (MOIs) were used to decrease and increase PTP1B expression in Raw 264.7 cells, respectively. mRNA and protein levels of TNF-α and IL-6 were measured by real-time PCR and ELISA, respectively.

Results

0.5 mM palmitate reduced PTP1B mRNA and protein levels by 25 and 19 %, respectively, compared to untreated cells. Overexpression of PTP1B decreased mRNA and protein levels of TNF-α and IL-6 in macrophages stimulated with palmitate. We found that protein and mRNA levels of cytokines significantly increased in knockdown cells stimulated by palmitate in a dose-dependent manner with increased MOI. NF-kB, JNK, p38 and ERK specific inhibitors significantly reduced the production of TNF-α and IL-6 in macrophages stimulated with palmitate and also PTP1B knockdown cells. Furthermore, inhibition of PTP1B resulted in increased phosphorylation of JNK, p38, ERK and NF-kB p65 in macrophage cells.

Conclusions

The data of this study demonstrate that PTP1B negatively regulates palmitate-induced cytokine secretion in macrophages by mechanisms involving the activation of MAPKs and NF-kB pathways.

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Abbreviations

ERK:

Extracellular-signal-regulated kinases

JNK:

C-Jun N-terminal kinase

INF-γ:

Interferon gamma

IL-6:

Interleukin 6

MAPK:

Mitogen-activated protein kinase

NF-kB:

Nuclear factor-kappa B

PTP1B:

Protein tyrosine phosphatase 1B

TRL:

Toll-like receptor

TNF-α:

Tumor necrosis factor α

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Acknowledgments

We thank Professor Mary K. Collins, UCL, London, UK for providing the plasmids.

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Authors and Affiliations

  1. The Department of Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran

    Ahmad Nasimian, Gholamreza Taheripak, Sattar Gorgani-Firuzjaee, Asie Sadeghi & Reza Meshkani

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  1. Ahmad Nasimian
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  2. Gholamreza Taheripak
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  3. Sattar Gorgani-Firuzjaee
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  5. Reza Meshkani
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Correspondence to Reza Meshkani.

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Responsible editor: Liwu Li

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Nasimian, A., Taheripak, G., Gorgani-Firuzjaee, S. et al. Protein tyrosine phosphatase 1B (PTP1B) modulates palmitate-induced cytokine production in macrophage cells. Inflamm. Res. 62, 239–246 (2013). https://doi.org/10.1007/s00011-012-0573-0

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  • DOI: https://doi.org/10.1007/s00011-012-0573-0

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