Oncotarget

Research Papers: Immunology:

Inhibitor of Tec kinase, LFM-A13, decreases pro-inflammatory mediators production in LPS-stimulated RAW264.7 macrophages via NF-κB pathway

Fei Wang, Wei Zhang, Chao Wang, Xu Fang, Hao Cheng, Sheng Liu and Xu-Lin Chen _

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Oncotarget. 2017; 8:34099-34110. https://doi.org/10.18632/oncotarget.16212

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Abstract

Fei Wang1,*, Wei Zhang2,*, Chao Wang1,*, Xu Fang1, Hao Cheng1, Sheng Liu1 and Xu-Lin Chen1

1 Department of Burns, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, PR China

2 Department of Nephrology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, PR China

* These authors have contributed equally to this work and are joint first authors

Correspondence to:

Xu-Lin Chen, email:

Keywords: lipopolysaccharide, Tec kinase, NF-κB, macrophages, Immunology and Microbiology Section, Immune response, Immunity

Received: June 03, 2016 Accepted: March 03, 2017 Published: March 15, 2017

Abstract

Tec kinase, a prototypical member of the Tec tyrosine kinases family, was shown to mainly govern lymphocyte proliferation. In the present study, we investigated the role of Tec kinase in acute inflammatory response in lipopolysaccharide (LPS) challenge. First, we demonstrate that Tec kinase activity was observed in RAW264.7 macrophages exposed to LPS. Tec and phosphorylated Tec expression were upregulated in a dose- and time-dependent manner after LPS stimulation. LPS increased monocyte chemotactic protein (MCP)-1 secretion and intercellular adhesion molecule (ICAM)-1 expression, and increasing mRNA expression was consistently observed. LPS also induced IκBα phoshporylaytion and its degradation, increased NF-κB p65 phoshporylaytion and translocation to nuclei in RAW264.7 cells. Pretreatment with LFM-A13 decreased LPS-induced cytokines and chemokines production and mRNA levels, blocked NF-κB transactivation. These effects of LPS were also prevented by Tec-siRNA. Additionally, LFM-A13 or Tec-siRNA obviously inhibited LPS-induced TGFβ-activated kinase 1(TAK1) phosphorylation. Taken together, our results suggest that Tec kinase involves in acute inflammation process in LPS-stimulated RAW264.7 cells, at least mediated by activating TAK1/ NF-κB signal pathway.


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