Rhinovirus-induced IL-1? release from bronchial epithelial cells is independent of functional P2X7.

ABSTRACT: Airway epithelial cell defenses to viral infections are often compromised in disease or injury. Danger molecules, including ATP, are released during infection and contribute to nucleotide receptor-dependent inflammatory responses, largely through P2X(7). Although respiratory epithelium has been shown to express a variety of nucleotide receptors, the functional contribution of P2X(7) to the epithelial cell inflammatory response is unclear. We used human donor bronchial epithelial cells (BECs) and primary brushed epithelium to explore responses upon nucleotide and Toll-like receptor stimulation. P2X(7) messenger RNA and protein were observed in unprimed BECs, whereas inflammatory cytokine stimulation increased both messenger RNA and protein. Functional pore activity characteristic of P2X(7) was observed in BECs, and IL-1? was rapidly released by BECs after Toll-like receptor 3 agonist, polyinosine-polycytidylic acid, priming followed by ATP administration, although no change was observed in IL-18 release. BECs produced more IL-1? after stimulation with polyinosine-polycytidylic acid than LPS, showing a different preferential response than monocytes. In addition, blockade of nucleotide receptors with oxidized ATP significantly increased human rhinovirus (HRV) recovered 24 hours after infection in BECs, whereas 2'-3'-O-(4-benzoylbenzoyl) ATP treatment of brushed epithelial cells and respiratory cell lines nonsignificantly decreased HRV recovery. IL-1? release was detected after HRV infection in both BECs and brushed cells, but BzATP did not significantly increase IL-1? release further. BEC processing of pro-IL-1? to the mature, cleaved, 17-kD form was confirmed by Western blotting. These results support the expression of functional P2X(7) in human lung epithelium, although its role in epithelial pathogen defense is likely independent of IL-1 family cytokine processing.

SUBMITTER: Shi L 

PROVIDER: S-EPMC3488691 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature