Expression of Plasminogen Activator Inhibitor 2 (PAI-2) in Response to Rhinovirus Infection

Abstract

RATIONALE: PAI-2 a cytoplasmic serine protease inhibitor with antiviral activity in some systems is upregulated in rhinovirus 1A (RV1A) infected primary bronchial epithelial cells (HBECs). We determined whether viral infection by minor and major group RV induced PAI-2 expression in vitro and by the major group in vivo. METHODS: For in vitro study, HBECs isolated from normal donors were incubated in medium with or without IFN-γ for 24 hr, then incubated with medium alone, or with minor or major group RV (MOI=10). Supernatant was collected and PAI-2 protein was assayed by ELISA. For in vivo study, nasal lavage fluid (NLF) from individuals inoculated with RV16 was collected and assayed for PAI-2 protein by ELISA and western blotting. RESULTS: PAI-2 was high in unstimulated cells, and was induced by minor group RV (RV1A and RV2; n=7, p # 0.01), but not by major group RV (RV16 and RV14; n=7). Pre-treating cells with IFN-γ significantly enhanced PAI-2 secretion in response to either minor or major group RV (n=7, p # 0.05). PAI-2 level was high in NLF and was significantly increased 3-7 days after infection (> 2.7 fold, n= 5, p<0.05). PAI-2 in NLF as detected by western blotting was increased and present in at least 2 forms at day 4 after infection. CONCLUSIONS: PAI-2 is expressed at high levels and is further increased by viral infection both in vivo and in vitro. IFN-γ is a cofactor in inducing PAI-2 expression. High-level expression and further upregulation by viral infection suggest that PAI-2 may have important anti-viral activities.