Yangyang Yu, Bo Yu, Weizhen Zhang, Wei Zhang, Zhangang Xiao, Zhuo Mao, Yihong Lai, Dongxu Lin, Qiang Ma, En Pan, Yarui Zhang and Meiling Jin
Shenzhen University Health Science Center, China
Peking University Shenzhen Hospital, China
Shenzhen PKU-HKUST Medical Center, China
Southwest Medical University, China
Toll-like receptors (TLRs) expressed on mast cells are essential for effective host defense against a wide variety of pathogens. Previous studies have demonstrated that TLR2 agonists Pam3CSK4 and PGN both stimulated IL-8 release in human mast cells. To determine the molecular basis for this phenomenon, we utilized a human mast cell line LAD2 cells. We found that only release of IL-8 stimulated by Pam3CSK4 was TLR2-mediated, which was confirmed by specific TLR2 shRNA. Heterotrimeric G proteins have been previously implicated in TLRs signaling in macrophages and monocytes. In the current study, we showed that PamCSK4 induced the activation of MAPKs, NF-κB, PI3K-Akt and Ca2+-calcineurin-NFAT signaling cascades in LAD2 cells. Go proteins were required for the activation of MAPKs and NF-κB in TLR2 stimulated LAD2 cells. Therefore, genetic depletion of Gαo proteins also leaded to reduction of IL-8 release in LAD2 cells. Taken together, the data presented here suggest that TLR2 activation in human mast cells promotes the release of inflammatory mediators via distinct signaling pathways that partially depends on Go protein action.
Yangyang Yu is a Professor at the Center for Diabetes, Obesity and Metabolism in the Department of Physiology, Shenzhen University Health Science Center of Guangdong province, China. She has published more than 20 papers in reputed journals and has been serving as an Editorial Board Member of repute.
Email: echoyyyu@163.com
