The p38 MAPK inhibitor SB203580 differentially modulates LPS-induced interleukin 6 expression in macrophages

Qinghai Shi; Liping Cheng; Zhengxiang Liu; Keyan Hu; Jihua Ran; Di Ge; Jianfeng Fu

doi:10.5114/ceji.2015.54586

eISSN: 1644-4124
ISSN: 1426-3912

Central European Journal of Immunology

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3/2015
vol. 40

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abstract:

Experimental immunology

The p38 MAPK inhibitor SB203580 differentially modulates LPS-induced interleukin 6 expression in macrophages

Qinghai Shi

,

Liping Cheng

,

Zhengxiang Liu

,

Keyan Hu

,

Jihua Ran

,

Di Ge

,

Jianfeng Fu

(Cent Eur J Immunol 2015; 40 (3): 276-282)

DOI: https://doi.org/10.5114/ceji.2015.54586

Online publish date: 2015/10/15

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The p38 mitogen-activated protein kinase (MAPK) plays a key role in lipopolysaccharide (LPS)-induced signal transduction pathways that lead to inflammatory cytokine synthesis in macrophages; however, whether the inhibition of p38 MAPK regulates LPS-induced inflammatory cytokine expression in different types of macrophages remains the subject of debate. Herein, we assessed whether the inhibition of p38 MAPK by SB203580 regulates LPS-induced expression of the inflammatory cytokines tumor necrosis factor  (TNF-) and interleukin 6 (IL-6) in RAW264.7 and resident peritoneal macrophages. Lipopolysaccharide stimulation of RAW264.7 macrophages or mouse resident peritoneal macrophages significantly increased TNF- and IL-6 production. The addition of SB203580 to cultures dramatically blocked LPS-induced TNF- production in RAW264.7 and mouse resident peritoneal macrophages, and dramatically blocked LPS-induced IL-6 production in RAW264.7 macrophages, but not in mouse resident peritoneal macrophages. Additionally, high concentrations of SB203580 resulted in increased IL-6 production. However, LPS-stimulation significantly up-regulated the mRNA transcript levels of TNF- and IL-6 in RAW264.7 and mouse resident peritoneal macrophages, whereas pretreatment with SB203580 dramatically down-regulated LPS-induced mRNA transcript levels of TNF- and IL-6 in these cells. Our data show that SB203580 differentially modulates LPS-induced production of the inflammatory cytokine IL-6 in two different sources of macrophages, and that this course of regulation occurs at the IL-6 mRNA post-transcriptional stage.

keywords:

The p38 MAPK inhibitor SB203580 differentially modulates LPS-induced interleukin 6 expression in macrophages

Qinghai Shi , Liping Cheng , Zhengxiang Liu , Keyan Hu , Jihua Ran , Di Ge , Jianfeng Fu

p38, interleukin 6, cytokine, lipopolysaccharide, macrophage

Qinghai Shi

,

Liping Cheng

,

Zhengxiang Liu

,

Keyan Hu

,

Jihua Ran

,

Di Ge

,

Jianfeng Fu