title: Mycoplasma hyopneumoniae-derived lipid-associated membrane proteins induce inflammation and apoptosis in porcine peripheral blood mononuclear cells in vitro.
abstract: Mycoplasma hyopneumoniae is the causative agent of swine enzootic pneumonia (EP), a disease that causes considerable economic losss in swine industry. Lipid-associated membrane proteins (LAMPs) of mycoplasma play important roles in causing mycoplasma diseases. The present study explores the pathogenic mechanisms of M. hyopneumoniae LAMPs by elucidating their role in modulating the inflammation, apoptosis, and relevant signaling pathways of peripheral blood mononuclear cells (PBMCs) of pig. LAMP treatment inhibited the growth of PBMCs. Up-regulation of cytokines, such as IL-6 and IL-1β, as well as increased production of nitric oxide (NO) and superoxide anion were all detected in the supernatant of LAMPs-treated PBMCs. Furthermore, flow cytometric analysis using dual staining with annexin-V-FITC and propidium iodide (PI) showed that LAMPs of M. hyopneumoniae induced a time-dependent apoptosis in lymphocyts and monocytes from PBMCs, which was blocked by NOS inhibitor or antioxidant. In addition, LAMPs induced the phosphorylation of p38, the ratio of pro-apoptotic Bax protein to anti-apoptotic Bcl-2, activation of caspase-3 and caspase-8, and poly ADP-ribose polymerase (PARP) cleavage in PBMCs. These findings demonstrated that M. hyopneumoniae LAMPs induced the production of proinflammatory cytokines, NO and reactive oxygen species (ROS), and apoptosis of PBMCs in vitro through p38 MAPK and Bax/Bcl-2 signaling pathways, as well as caspase activation.
authors.affiliation: Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, National Center for Engineering Research of Veterinary Bio-products, Nanjing 210014, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Bai
authors.affiliation: Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, National Center for Engineering Research of Veterinary Bio-products, Nanjing 210014, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Ni
authors.affiliation: Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, National Center for Engineering Research of Veterinary Bio-products, Nanjing 210014, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
authors.forename: Maojun
authors.initials: M
authors.lastname: Liu
authors.affiliation: Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, National Center for Engineering Research of Veterinary Bio-products, Nanjing 210014, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, National Center for Engineering Research of Veterinary Bio-products, Nanjing 210014, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
authors.forename: Qiyan
authors.initials: Q
authors.lastname: Xiong
authors.affiliation: Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, National Center for Engineering Research of Veterinary Bio-products, Nanjing 210014, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China. Electronic address: gqshaojaas@gmail.com.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Shao
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation; D007249:Inflammation / Q000662:veterinary; D015850:Interleukin-6 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000382:microbiology* / Q000502:physiology; D008055:Lipids; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D045705:Mycoplasma hyopneumoniae / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D045729:Pneumonia of Swine, Mycoplasmal / Q000276:immunology* / Q000382:microbiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013552:Swine; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D008055:Lipids; D008565:Membrane Proteins; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D009569:Nitric Oxide; D053148:Caspase 3; D053181:Caspase 8
keywords: Apoptosis; Lipid-associated membrane proteins; Mycoplasma hyopneumoniae; Peripheral blood mononuclear cells