Chunling Dong

Anti-asthmatic agents alleviate pulmonary edema by upregulating AQP1 and AQP5 expression in the lungs of mice with OVA-induced asthma.

Ovalbumin (OVA)-induced asthma in mouse lungs causes changes in the mRNA and protein levels of aquaporins (AQPs). AQP expression was examined in the presence of various anti-asthmatic agents, including dexamethasone, ambroxol, and terbutaline. The influence of these agents on OVA-induced airway inflammation was also evaluated. The mRNA expression levels of AQP1, 4, and 5 were significantly reduced and that of AQP3 was significantly increased 24h after the last OVA exposure. The protein levels of AQP1, 3, and 5 mirrored the mRNA expression profiles, but AQP4 did not exhibit any changes. Only the mRNA and protein expression levels of AQP1 and AQP5 were significantly increased by these three anti-asthmatic agents. Dexamethasone and ambroxol improved the eosinophil infiltration, mucus secretion, and pulmonary edema caused by OVA, but terbutaline only alleviated pulmonary edema. These results indicate that AQP1 and AQP5 are closely related to pulmonary edema but not to eosinophil infiltration or mucus secretion during asthma. Anti-asthmatic agents could alleviate pulmonary edema through upregulating the expression of AQP1 and AQP5 in mouse lungs that have OVA-induced asthma.

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.