TLR4-mediated IRAK1 activation induces TNF-alpha expression via JNK-dependent NF-kappa B activation in human bronchial epithelial cells
- Authors
- Park, Sae Hoon; Choi, Hye-Jin; Lee, So Young; Han, Joong-Soo
- Issue Date
- Dec-2015
- Publisher
- Biolife
- Keywords
- IRAK1; JNK; NF-kappa B; TLR4; TNF-alpha
- Citation
- European Journal of Inflammation, v.13, no.3, pp 183 - 195
- Pages
- 13
- Journal Title
- European Journal of Inflammation
- Volume
- 13
- Number
- 3
- Start Page
- 183
- End Page
- 195
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/10090
- DOI
- 10.1177/1721727X15619185
- ISSN
- 1721-727X
2058-7392
- Abstract
- The purpose of this study was to identify the mechanism of lipopolysaccharide (LPS)-induced expression of tumor necrosis factor (TNF)-alpha in BEAS-2B. Toll-like receptor (TLR)4-specific siRNA was found to completely abolish the LPS-induced expression of MyD88 and TNF-alpha. There was enhanced binding of MyD88 with IRAK1 following LPS treatment, and MyD88- or IRAK1-specific siRNAs decreased the expression of TNF-alpha. In addition, IRAK1 siRNA downregulated the phosphorylation of PKC alpha, demonstrating that PKC alpha is a downstream effector of IRAK1. Inhibition of PKC alpha completely blocked the activation of AKT, whereas inhibition of AKT with a PI3K inhibitor prevented the LPS-induced expression of TNF-alpha. We found that AKT activated JNK, which then stimulated phosphorylation of I kappa-B alpha, resulting in NF-kappa B activation. As expected, inhibition of NF-kappa B completely inhibited the expression of TNF-alpha. Taken together, our results suggest that LPS induces TNF-alpha expression by activating NF-kappa B via the PKC/PI3K/AKT/JNK pathway, which is in turn dependent on MyD88/IRAK1.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - College of Medicine > Department of Emergency Medicine > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/10090)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.