, Volume 62, Issue 2, pp 239-246
Date: 15 Nov 2012

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.

Responsible editor: Liwu Li