Effect of cyclooxygenase-2 inhibition on lung inflammation and hypoxia-inducible factor-1 signalling in COPD model

There is an opinion, that the local inhibition of hypoxia-inducible factor-1α (HIF-1α) in lung may represent a therapeutic strategy for the treatment of inflammatory pulmonary diseases. Aim: to evaluate the modifying effect of cyclooxygenase-2 (COX-2) inhibition on lung inflammation and change of HIF-1α in COPD model. Methods: Model of COPD was induced in rats by nitrogen dioxide (15-19 ppm) exposure: three 30-min exposures/day with 30-min intervals for 60 days. Celecoxib (C) was used as a COX-2 inhibitor. From 30th to 60th day rats of 1st group received C via esophageal probe, rats of 2nd group (control) received 0,9% NaCl. 3rd group was intact. Bronchoalveolar lavage fluid (BALF) cytogram was determined. The levels of COX-2, HIF-1α, IL-17, surfactant protein D (SP-D) were measured in BALF by ELISA. Results: Treatment with C decreased COX-2 level in BALF: 18,8±2,2 vs. 26,5±2,3 pg/ml in control group, p Conclusion: The inhibition of COX-2 had a supressive effect on lung inflammation. It can be assumed that COX-2-dependent mechanism is involved in the inhibition of HIF-1α signalling, that can contribute to restoring the structure of bronchial epithelium.