Expression of heme oxygenase in human airway epithelial cells

Elevated levels of carbon monoxide (CO) are found in the exhaled breath of patients with inflammatory diseases such as asthma and cystic fibrosis. End ogenous CO is derived from heme oxygenase (HO) (EC 1.14.99.3), which catabo lizes heme-producing CO and biliverdin. There are three isoforms of HO: HO- 1 is inducible by inflammatory cytokines and oxidants, including nitric oxi de (NO), whereas HO-2 and HO-3 are expressed constitutively. Primary airway epithelial cells were treated with either 50 ng/ml interleukin-1 beta, tum or necrosis factor-alpha, and interferon-gamma (cytomix), or the NO donor N OC-18 for up to 24 h. Cytomix-induced HO-1 expression peaked at 4 h, return ing to baseline by 24 h, whereas HO-2 expression remained unchanged. This i ncrease in HO-1 expression could not be explained by an increase in NO prod uction as inducible NO synthase expression increased between 12 and 24 h. H owever, the NO donor NOC-18 (500 muM) increased HO-1 expression twofold and HO activity 25-fold, whereas cytomix treatment increased HO activity eight fold. NO induction of HO-1 was not mediated via guanylyl cyclase and was no t attenuated by 1 muM dexamethasone, although dexamethasone increased HO-2 protein. Therefore, airway epithelial cells express HO-2 and can express HO -1; thus, the epithelium may be a source of increased CO in airway diseases .