TLR4-mediated IRAK1 activation induces TNF-α expression via JNK-dependent NF-κB activation in human bronchial epithelial cells

European Journal of Inflammation

Original articles

So Young Lee¹  Joong-Soo Han¹  Hye-Jin Choi¹  Sae Hoon Park² 

[1] Biomedical Research Institute and Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul, Republic of Korea;Department of Emergency Medicine, Soon Chun Hyang University, Cheonan Hospital, Cheonan, Republic of Korea;

关键词: IRAK1;    JNK;    NF-κB;    TLR4;    TNF-α;   

DOI  :  10.1177/1721727X15619185

 received in 2015-06-30, accepted in 2015-11-04,  发布年份 2015

来源: Sage Journals

【 摘 要 】

The purpose of this study was to identify the mechanism of lipopolysaccharide (LPS)-induced expression of tumor necrosis factor (TNF)-α in BEAS-2B. Toll-like receptor (TLR)4-specific siRNA was found to completely abolish the LPS-induced expression of MyD88 and TNF-α. There was enhanced binding of MyD88 with IRAK1 following LPS treatment, and MyD88- or IRAK1-specific siRNAs decreased the expression of TNF-α. In addition, IRAK1 siRNA downregulated the phosphorylation of PKCα, demonstrating that PKCα is a downstream effector of IRAK1. Inhibition of PKCα completely blocked the activation of AKT, whereas inhibition of AKT with a PI3K inhibitor prevented the LPS-induced expression of TNF-α. We found that AKT activated JNK, which then stimulated phosphorylation of Iκ-Bα, resulting in NF-κB activation. As expected, inhibition of NF-κB completely inhibited the expression of TNF-α. Taken together, our results suggest that LPS induces TNF-α expression by activating NF-κB via the PKCα/PI3K/AKT/JNK pathway, which is in turn dependent on MyD88/IRAK1.

【 授权许可】

Unknown   
© The Author(s) 2015

【 图 表 】

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