title: Role of toll-like receptor 4 in acute neutrophilic lung inflammation induced by intratracheal bacterial products in mice.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  These results suggest that TLR4 mediates inflammatory cascade induced by Gram-negative bacteria that is locally administered.
authors.affiliation: Division of Pulmonary Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Wakako
authors.initials: W
authors.lastname: Yamada
authors.forename: Sadatomo
authors.initials: S
authors.lastname: Tasaka
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Koh
authors.forename: Mie
authors.initials: M
authors.lastname: Shimizu
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Hasegawa
authors.forename: Taku
authors.initials: T
authors.lastname: Miyasho
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Ishizaka
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