G_o is required for the release of IL-8 and TNF-α, but not degranulation in human mast cells

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• 作者：Yangyang Yu^a ; Zhenhe Huang^d ; Zhuo Mao^a ; Yarui Zhang^c ; Meiling Jin^a ; Wenwen Chen^a ; Wei Zhang^c ; Bo Yu^b ; ¹ ; ^{yubomd@163.com" class="auth_mail" title="E-mail the corresponding author} ; Weizhen Zhang^a ; ¹ ; ^{weizhenz@umich.edu" class="auth_mail" title="E-mail the corresponding author} ; Hang Yung Alaster Lau^e
• 关键词：Akt ; Protein kinase B ; BAC ; Benzalkonium chloride ; FcεRI ; High-affinity receptor for IgE ; G protein ; Guanine nucleotide-binding protein ; GPCRs ; Gprotein-coupled receptors ; JNK ; c-Jun N-terminal kinase ; LAD2 cells ; Laboratory of allergic disease 2 human mast cells ; PLC ; Phospholipase C ; PTX ; Pertussis toxin
• 刊名：European Journal of Pharmacology
• 出版年：2016
• 出版时间：5 June 2016
• 年：2016
• 卷：780
• 期：Complete
• 页码：115-121
• 全文大小：1408 K

文摘

Mast cells activated by IgE-dependent and -independent mechanisms play important roles in innate and acquired immune responses. Activation of pertussis toxin (PTX)-sensitive G_i/o proteins is the key step in mast cell degranulation and release of de novo synthesized inflammatory mediators through IgE-independent mechanism. However, the roles of G_i and G_o proteins in mast cells activation have not yet been differentiated. In the current study, the functional roles of G_o proteins in the activities of LAD2 cells, a human mast cell line, are identified. Knockdown of Gα_o expression significantly inhibited the synthesis of IL-8 and TNF-α from substance P activated LAD2 cells but demonstrated no effect on degranulation. This effect was associated with the activation of Erk and JNK/MAPKs signaling, whereas PI3K-Akt, calcium mobilization and NFAT translocation remained unchanged. These results suggest that G_i and G_o proteins differentially regulate human mast cells activities through activating distinct signaling cascades.