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Infect. Immun. doi:10.1128/IAI.00955-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Mycoplasma pneumoniae-derived Lipopeptides Induce Acute Inflammatory Responses in the Lungs of Mice

Takashi Shimizu, Yutaka Kida, and Koichi Kuwano*

The Division of Microbiology, Department of Infectious Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan

* To whom correspondence should be addressed. Email: kuwano{at}med.kurume-u.ac.jp.


   Abstract

The pathogenesis of Mycoplasma pneumoniae infection is considered to be in part attributed to excessive immune responses. In this study, we investigated whether synthetic lipopeptides of subunit b of F0F1-type ATPase (F0F1-ATPase), NF-{kappa}B-activating lipoprotein (N-ALP) 1, 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 (BALF), 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 (TNF) {alpha} through TLR2 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 M. fermentans and M. 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




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