Yan Meng1, Chen Chen, Lei Wang, Xia Wang, Cui Tian, Jie Du, Hui-Hua Li. 1. Department of Pathology, Physiology and Pathophysiology, AnZhen Hospital the Key Laboratory of Remodeling-Related Cardiovascular Diseases, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
Abstract
BACKGROUND: Peptidoglycan (PGN) is a component of cell wall in Gram-positive bacteria that stimulates inflammatory responses through Toll-like receptor 2 (TLR2). The carboxyl terminus of constitutive heat shock cognate 70 (HSC70)-interacting protein (CHIP, also known as Stub1) is a U-box-type E3 ubiquitin ligase, which plays an important role in protein quality control and inflammation through ubquitin-mediated proteasomal degradation. However, it is unclear whether TLR2 agonist PGN regulates the expression and activation of CHIP. METHODS/ RESULTS: In this study, we showed that PGN significantly up-regulated the expression of CHIP in both mRNA and protein levels in RAW264.7 cells in a time-dependant manner, and the expression of CHIP induced by PGN was abolished in TLR2 knockout macrophages. No significant change in CHIP was observed after lipopolysaccharide (LPS, TLR4 agonist) and cytosine-phosphorous-guanine oligonucleotide (CpG ODN, TLR9 agonist) treatment. Moreover, PGN markedly induced the expression and activity of CHIP in macrophages, whereas this effect was attenuated by SP600125, a selective inhibitor of JNK. CONCLUSION: Our study for the first time demonstrates that TLR2 activation enhances the expression and activity of CHIP through JNK signaling pathway.
BACKGROUND: Peptidoglycan (PGN) is a component of cell wall in Gram-positive bacteria that stimulates inflammatory responses through Toll-like receptor 2 (TLR2). The carboxyl terminus of constitutive heat shock cognate 70 (HSC70)-interacting protein (CHIP, also known as Stub1) is a U-box-type E3 ubiquitin ligase, which plays an important role in protein quality control and inflammation through ubquitin-mediated proteasomal degradation. However, it is unclear whether TLR2 agonist PGN regulates the expression and activation of CHIP. METHODS/ RESULTS: In this study, we showed that PGN significantly up-regulated the expression of CHIP in both mRNA and protein levels in RAW264.7 cells in a time-dependant manner, and the expression of CHIP induced by PGN was abolished in TLR2 knockout macrophages. No significant change in CHIP was observed after lipopolysaccharide (LPS, TLR4 agonist) and cytosine-phosphorous-guanine oligonucleotide (CpG ODN, TLR9 agonist) treatment. Moreover, PGN markedly induced the expression and activity of CHIP in macrophages, whereas this effect was attenuated by SP600125, a selective inhibitor of JNK. CONCLUSION: Our study for the first time demonstrates that TLR2 activation enhances the expression and activity of CHIP through JNK signaling pathway.
Authors: Chen Chen; Yan Meng; Lei Wang; Hong-Xia Wang; Cui Tian; Guo-Dong Pang; Hui-Hua Li; Jie Du Journal: Immunology Date: 2014-06 Impact factor: 7.397
Authors: Karyn E O'Connell; Wen Guo; Carlo Serra; Matthew Beck; Lynn Wachtman; Amber Hoggatt; Dongling Xia; Chris Pearson; Heather Knight; Micheal O'Connell; Andrew D Miller; Susan V Westmoreland; Shalender Bhasin Journal: FASEB J Date: 2014-12-02 Impact factor: 5.191