CORTICOSTEROIDS INDUCE INTRACELLULAR INTERLEUKIN-1 RECEPTOR ANTAGONIST TYPE-I EXPRESSION BY A HUMAN AIRWAY EPITHELIAL-CELL LINE

Interleukin-1 (IL-1) is an important proinflammatory cytokine which ma y contribute to the pathogenesis of inflammatory airway disorders, suc h as asthma and cystic fibrosis. Interleukin-1 receptor antagonist (IL -1ra) is a naturally occurring IL-1 inhibitor which binds to IL-1 rece ptors without inducing agonist activity. Three IL-1ra isoforms have be en identified: secreted IL-1ra (sIL-1ra), which is preferentially expr essed by inflammatory cells; intracellular IL-1ra (iIL-1ra) type I, wh ich lacks a signal peptide and is preferentially expressed by epitheli al cells; and ilL-1ra type II, which is identical to iIL-1ra type I ex cept for the insertion of an additional 21 amino acids. The goal of th is study was to assess whether airway epithelial cell iIL-1ra type I p roduction can be regulated by corticosteroids. First, using reverse tr anscription-polymerase chain reaction (RT-PCR) and immunoblotting, we confirm that normal human bronchial epithelial (NHBE) cells and a huma n pulmonary mucoepidermoid carcinoma cell line (NCI-H292) express intr acellular IL-1ra type I messenger RNA (mRNA) and protein. Second, usin g immunoblotting and ELISA, we report that dexamethasone induces time- and concentration-dependent increases in iIL-1ra type I protein withi n NCI-H292 cell lysates. Lastly, utilizing a ribonuclease protection a ssay, we report that dexamethasone induces concentration-dependent inc reases in iIL-1ra type I mRNA levels in NCI-H292 cells. These data sug gest that corticosteroid-mediated induction of iIL-1ra type I mRNA and protein by human bronchial epithelial cells represents a novel mechan ism by which IL-1-mediated airway inflammatory events might be regulat ed.