Role of toll-like receptor 4 in acute neutrophilic lung inflammation induced by intratracheal bacterial products in mice

Wakako Yamada1, Sadatomo Tasaka1, Hidefumi Koh1, Mie Shimizu1, Yuko Ogawa1, Naoki Hasegawa1, Taku Miyasho2, Kazuhiro Yamaguchi1, Akitoshi Ishizaka11Division of Pulmonary Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan; 2Laboratory of Veterinary Biochemistry, School of Veterin...

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Autores principales: Wakako Yamada, Sadatomo Tasaka, Hidefumi Koh, Mie Shimizu, Yuko Ogawa, et al
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Publicado: Dove Medical Press 2008
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spelling oai:doaj.org-article:9948281033aa44e3af7038d4f2fa782a2021-12-02T00:35:55ZRole of toll-like receptor 4 in acute neutrophilic lung inflammation induced by intratracheal bacterial products in mice1178-7031https://doaj.org/article/9948281033aa44e3af7038d4f2fa782a2008-09-01T00:00:00Zhttp://www.dovepress.com/role-of-toll-like-receptor-4-in-acute-neutrophilic-lung-inflammation-i-a2156https://doaj.org/toc/1178-7031Wakako Yamada1, Sadatomo Tasaka1, Hidefumi Koh1, Mie Shimizu1, Yuko Ogawa1, Naoki Hasegawa1, Taku Miyasho2, Kazuhiro Yamaguchi1, Akitoshi Ishizaka11Division of Pulmonary Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan; 2Laboratory of Veterinary Biochemistry, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, JapanBackground: Toll-like receptors (TLRs) represent a conserved family of innate immune recognition receptors. Among TLRs, TLR4 is important for the recognition of Gram-negative bacteria, whereas TLR2 recognizes cell wall constituents of Gram-positive microorganisms, such as peptidoglycan (PGN).Methods: To evaluate the role of TLR4 in the pathogenesis of acute lung injury induced by Escherichia coli endotoxin (lipopolysaccharide; LPS) or PGN, we compared inflammatory cell accumulation in bronchoalveolar lavage (BAL) fluid and lung pathology between C3H/HeJ (TLR4 mutant) and wild-type C3H/HeN mice. The levels of proinflammatory cytokines and chemokines in plasma and BAL fluid and nuclear factor-κB (NF-κB) translocation in the lung were also evaluated.Results: In C3H/HeJ mice, LPS-induced neutrophil emigration was significantly decreased compared with C3H/HeN mice, whereas PGN-induced neutrophil emigration did not differ. Differential cell count in BAL fluid revealed comparable neutrophil recruitment in the alveolar space. In TLR4 mutant mice, LPS-induced upregulation of tumor necrosis factor-alpha (TNF-α), KC, and CXCL10 in plasma and BAL fluid was attenuate, which was not different after PGN. NF-κB translocation in the lung was significantly decreased in C3H/HeJ compared with C3H/HeN mice, whereas PGN-induced NF-κB translocation was not different.Conclusion: These results suggest that TLR4 mediates inflammatory cascade induced by Gram-negative bacteria that is locally administered.Keywords: rodent, TLR4, endotoxin, neutrophils, NF-κB Wakako YamadaSadatomo TasakaHidefumi KohMie ShimizuYuko Ogawaet alDove Medical PressarticlePathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol 2008, Iss default, Pp 1-10 (2008)
institution DOAJ
collection DOAJ
language EN
topic Pathology
RB1-214
Therapeutics. Pharmacology
RM1-950
spellingShingle Pathology
RB1-214
Therapeutics. Pharmacology
RM1-950
Wakako Yamada
Sadatomo Tasaka
Hidefumi Koh
Mie Shimizu
Yuko Ogawa
et al
Role of toll-like receptor 4 in acute neutrophilic lung inflammation induced by intratracheal bacterial products in mice
description Wakako Yamada1, Sadatomo Tasaka1, Hidefumi Koh1, Mie Shimizu1, Yuko Ogawa1, Naoki Hasegawa1, Taku Miyasho2, Kazuhiro Yamaguchi1, Akitoshi Ishizaka11Division of Pulmonary Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan; 2Laboratory of Veterinary Biochemistry, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, JapanBackground: Toll-like receptors (TLRs) represent a conserved family of innate immune recognition receptors. Among TLRs, TLR4 is important for the recognition of Gram-negative bacteria, whereas TLR2 recognizes cell wall constituents of Gram-positive microorganisms, such as peptidoglycan (PGN).Methods: To evaluate the role of TLR4 in the pathogenesis of acute lung injury induced by Escherichia coli endotoxin (lipopolysaccharide; LPS) or PGN, we compared inflammatory cell accumulation in bronchoalveolar lavage (BAL) fluid and lung pathology between C3H/HeJ (TLR4 mutant) and wild-type C3H/HeN mice. The levels of proinflammatory cytokines and chemokines in plasma and BAL fluid and nuclear factor-κB (NF-κB) translocation in the lung were also evaluated.Results: In C3H/HeJ mice, LPS-induced neutrophil emigration was significantly decreased compared with C3H/HeN mice, whereas PGN-induced neutrophil emigration did not differ. Differential cell count in BAL fluid revealed comparable neutrophil recruitment in the alveolar space. In TLR4 mutant mice, LPS-induced upregulation of tumor necrosis factor-alpha (TNF-α), KC, and CXCL10 in plasma and BAL fluid was attenuate, which was not different after PGN. NF-κB translocation in the lung was significantly decreased in C3H/HeJ compared with C3H/HeN mice, whereas PGN-induced NF-κB translocation was not different.Conclusion: These results suggest that TLR4 mediates inflammatory cascade induced by Gram-negative bacteria that is locally administered.Keywords: rodent, TLR4, endotoxin, neutrophils, NF-κB
format article
author Wakako Yamada
Sadatomo Tasaka
Hidefumi Koh
Mie Shimizu
Yuko Ogawa
et al
author_facet Wakako Yamada
Sadatomo Tasaka
Hidefumi Koh
Mie Shimizu
Yuko Ogawa
et al
author_sort Wakako Yamada
title Role of toll-like receptor 4 in acute neutrophilic lung inflammation induced by intratracheal bacterial products in mice
title_short Role of toll-like receptor 4 in acute neutrophilic lung inflammation induced by intratracheal bacterial products in mice
title_full Role of toll-like receptor 4 in acute neutrophilic lung inflammation induced by intratracheal bacterial products in mice
title_fullStr Role of toll-like receptor 4 in acute neutrophilic lung inflammation induced by intratracheal bacterial products in mice
title_full_unstemmed Role of toll-like receptor 4 in acute neutrophilic lung inflammation induced by intratracheal bacterial products in mice
title_sort role of toll-like receptor 4 in acute neutrophilic lung inflammation induced by intratracheal bacterial products in mice
publisher Dove Medical Press
publishDate 2008
url https://doaj.org/article/9948281033aa44e3af7038d4f2fa782a
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