title: Go is required for the release of IL-8 and TNF-α, but not degranulation in human mast cells.
abstract: Mast cells activated by IgE-dependent and -independent mechanisms play important roles in innate and acquired immune responses. Activation of pertussis toxin (PTX)-sensitive Gi/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 Gi and Go proteins in mast cells activation have not yet been differentiated. In the current study, the functional roles of Go proteins in the activities of LAD2 cells, a human mast cell line, are identified. Knockdown of Gαo 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 Gi and Go proteins differentially regulate human mast cells activities through activating distinct signaling cascades.
authors.affiliation: School of medicine, Shenzhen University, Shenzhen, Guangdong Province 518060, China.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Geriatrics, The Sixth People's Hospital of Shenzhen, Guangdong Province, China.
authors.forename: Zhenhe
authors.initials: Z
authors.lastname: Huang
authors.affiliation: School of medicine, Shenzhen University, Shenzhen, Guangdong Province 518060, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Mao
authors.affiliation: Shenzhen Key Laboratory for Translational Medicine of Dermatology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Guangdong Province, China.
authors.forename: Yarui
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of medicine, Shenzhen University, Shenzhen, Guangdong Province 518060, China.
authors.forename: Meiling
authors.initials: M
authors.lastname: Jin
authors.affiliation: School of medicine, Shenzhen University, Shenzhen, Guangdong Province 518060, China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Chen
authors.affiliation: Shenzhen Key Laboratory for Translational Medicine of Dermatology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Guangdong Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China. Electronic address: yubomd@163.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Yu
authors.affiliation: School of medicine, Shenzhen University, Shenzhen, Guangdong Province 518060, China. Electronic address: weizhenz@umich.edu.
authors.forename: Weizhen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region.
authors.forename: Hang Yung
authors.initials: HY
authors.lastname: Alaster Lau
mesh_terms: D002118:Calcium / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013373:Substance P / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D016209:Interleukin-8; D050778:NFATC Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D013373:Substance P; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D002118:Calcium
keywords: Benzalkonium chloride (PubChem CID: 8755); G(i) protein; G(o) protein; GNAO1; GPCR; Mast cells; Substance P (PubChem CID: 36511)