title: Pulmonary epithelial CCR3 promotes LPS-induced lung inflammation by mediating release of IL-8.
abstract: Interleukin (IL)-8 from pulmonary epithelial cells has been suggested to play an important role in the airway inflammation, although the mechanism remains unclear. We envisioned a possibility that pulmonary epithelial CCR3 could be involved in secretion and regulation of IL-8 and promote lipopolysaccharide (LPS)-induced lung inflammation. Human bronchial epithelial cell line NCI-H292 and alveolar type II epithelial cell line A549 were used to test role of CCR3 in production of IL-8 at cellular level. In vivo studies were performed on C57/BL6 mice instilled intratracheally with LPS in a model of acute lung injury (ALI). The activity of a CCR3-specific inhibitor (SB-328437) was measured in both in vitro and in vivo systems. We found that expression of CCR3 in NCI-H292 and A549 cells were increased by 23% and 16%, respectively, 24 h after the challenge with LPS. LPS increased the expression of CCR3 in NCI-H292 and A549 cells in a time-dependent manner, which was inhibited significantly by SB-328437. SB-328437 also diminished neutrophil recruitment in alveolar airspaces and improved LPS-induced ALI and production of IL-8 in bronchoalveolar lavage fluid. These results suggest that pulmonary epithelial CCR3 be involved in progression of LPS-induced lung inflammation by mediating release of IL-8. CCR3 in pulmonary epithelia may be an attractive target for development of therapies for ALI.
authors.affiliation: Department of Pulmonary Medicine, Institute of Respiratory Disease, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.forename: Chunling
authors.initials: C
authors.lastname: Dong
authors.forename: Guifang
authors.initials: G
authors.lastname: Wang
authors.forename: Huiru
authors.initials: H
authors.lastname: Zheng
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Wang
authors.forename: Chunxue
authors.initials: C
authors.lastname: Bai
mesh_terms: D055371:Acute Lung Injury / Q000473:pathology; D000818:Animals; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000378:metabolism*; D007700:Kinetics; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009281:Naphthalenes / Q000494:pharmacology; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D011014:Pneumonia / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054397:Receptors, CCR3 / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: C515350:CCR3 protein, human; C508606:CXCL8 protein, human; D016209:Interleukin-8; D008070:Lipopolysaccharides; D009281:Naphthalenes; D012333:RNA, Messenger; D054397:Receptors, CCR3; C417503:SB 328437; D010649:Phenylalanine