Nitric oxide and prostaglandin response to group B streptococcal infection in the lung

Abstract

Group B streptococcus (GBS) causes a complex inflammatory process that involves prostaglandins (PG) and nitric oxide (NO). The goal of this study was to examine the inflammatory response to GBS in the lung and the co-regulation of the PG and NO pathways, if any, both in vitro and in vivo. Sprague Dawley rats were treated with various combinations of GBS, aminoguanidine (AG), a selective inducible nitric oxide synthase (iNOS) inhibitor, and L-arginine (LA), a NO donor. The mRNA expression of the COX 2 gene was studied by reverse transcriptase polymerase chain reaction (RTPCR) in rat lung tissue. The studies were confirmed in vitro using human lung epithelial (A549) cells treated with GBS, AG, and LA (in combinations similar to the rats) for 3 and 24 hr, after which PG E2 levels in the media were measured by enzyme linked immunosorbent assay (ELISA). COX 2 mRNA in rat lung tissue was significantly induced by GBS (p = 0.04), an effect that was suppressed by AG (p = 0.02). In the A549 cell line, PG E2 levels increased with GBS treatment at 3 and 24 hr (p <0.001). When AG was added, PG E2 levels were suppressed (p = 0.03) after 24 hr; LA partly reversed the suppression of PG E2 levels (p = 0.039). These data indicate that GBS infection causes significant COX 2 induction and PG E2 synthesis in lung tissue, regulated at least partly by the NO pathway. The interaction between the 2 pathways may play a pathogenic role in GBS lung infections and could be a potential target for pharmacological manipulation.