title: Apoptosis and pro-inflammatory cytokine response of mast cells induced by influenza A viruses.
abstract: The pathogenesis of the influenza A virus has been investigated heavily, and both the inflammatory response and apoptosis have been found to have a definitive role in this process. The results of studies performed by the present and other groups have indicated that mast cells may play a role in the severity of the disease. To further investigate cellular responses to influenza A virus infection, apoptosis and inflammatory response were studied in mouse mastocytoma cell line P815. This is the first study to demonstrate that H1N1 (A/WSN/33), H5N1 (A/Chicken/Henan/1/04), and H7N2 (A/Chicken/Hebei/2/02) influenza viruses can induce mast cell apoptosis. They were found to do this mainly through the mitochondria/cytochrome c-mediated intrinsic pathway, and the activation of caspase 8-mediated extrinsic pathway was here found to be weak. Two pro-apoptotic Bcl-2 homology domain 3 (BH3) -only molecules Bim and Puma appeared to be involved in the apoptotic pathways. When virus-induced apoptosis was inhibited in P815 cells using pan-caspase (Z-VAD-fmk) and caspase-9 (Z-LEHD-fmk) inhibitors, the replication of these three subtypes of viruses was suppressed and the secretions of pro-inflammatory cytokines and chemokines, including IL-6, IL-18, TNF-α, and MCP-1, decreased. The results of this study may further understanding of the role of mast cells in host defense and pathogenesis of influenza virus. They may also facilitate the development of novel therapeutic aids against influenza virus infection.
authors.affiliation: Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Di
authors.initials: D
authors.lastname: Meng
authors.affiliation: Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Tangting
authors.initials: T
authors.lastname: Wei
authors.affiliation: Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Siyi
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Yanxin
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China; Zhongmu Institutes of China Animal Husbandry Group, Beijing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D029521:Alphainfluenzavirus / Q000472:pathogenicity*; D008407:Mast Cells / Q000378:metabolism / Q000821:virology*; D051379:Mice
chemical_list: D051017:Apoptosis Regulatory Proteins; D016207:Cytokines