Pulmonary epithelial CCR3 promotes LPS-induced lung inflammation by mediating release of IL-8

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. J. Cell. Physiol. 226: 2398–2405, 2011. © 2010 Wiley‐Liss, Inc.