title: Mycoplasma pneumoniae-derived lipopeptides induce acute inflammatory responses in the lungs of mice.
abstract: The pathogenesis of Mycoplasma pneumoniae infection is considered to be in part attributable to excessive immune responses. In this study, we investigated whether synthetic lipopeptides of subunit b of F0F1-type ATPase (F0F1-ATPase), NF-kappaB-activating lipoprotein 1 (N-ALP1), and N-ALP2 (named FAM20, sN-ALP1, and sN-ALP2, respectively) derived from M. pneumoniae induce cytokine and chemokine production and leukocyte infiltration in vivo. Intranasal administration of FAM20 and sN-ALP2 induced infiltration of leukocyte cells and production of chemokines and cytokines in bronchoalveolar lavage fluid, but sN-ALP1 failed to do so. The activity of FAM20 was notably higher than that of sN-ALP2. FAM20 and sN-ALP2 induced tumor necrosis factor alpha (TNF-alpha) through Toll-like receptor 2 in mouse peritoneal macrophages. Moreover, in the range of low concentrations of lipopeptides, FAM20 showed relatively high activity of inducing TNF-alpha in mouse peritoneal macrophages compared to synthetic lipopeptides such as MALP-2 and FSL-1, derived from Mycoplasma fermentans and Mycoplasma salivarium, respectively. These findings indicate that the F0F1-ATPase might be a key molecule in inducing cytokines and chemokines contributing to inflammatory responses during M. pneumoniae infection in vivo.
authors.affiliation: Division of Microbiology, Department of Infectious Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimizu
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kida
authors.forename: Koichi
authors.initials: K
authors.lastname: Kuwano
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D016207:Cytokines; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced*; D007962:Leukocytes; D008074:Lipoproteins / Q000008:administration & dosage / Q000138:chemical synthesis / Q000378:metabolism / Q000633:toxicity*; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009177:Mycoplasma pneumoniae / Q000378:metabolism*; D011487:Protein Conformation
chemical_list: D016207:Cytokines; D008074:Lipoproteins