Abstract
Background: NADPH oxidase (NOX) plays an important role in inflammatory responses by producing reactive oxygen species. The inhibition of NOX has been shown to participate in anti-inflammatory action in some inflammatory models. The aim of this study was to investigate the effects of diphenyleneiodonium (DPI), a NOX inhibitor, on lipopolysaccharide (LPS)-induced acute lung injury (ALI) model.
Methods: Sprague Dawley rats were intraperitoneally administered DPI (5 mg/kg) 30 minutes after intratracheal instillation with LPS (3 mg/kg). After 6 hours, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. The numbers of inflammatory cells and cytokine release (TNF-α, IL-1β, and IL-6) in BALF were detected by cell counting and ELISA. In lung tissues, NF-κB, myeloperoxidase (MPO) activity and ALI score were measured. Inducible nitric oxide synthase (iNOS) was examined by immunohistochemistry. To identify the anti-inflammatory mechanism of DPI, activation of MAPK and NF-κB pathways was measured by western blot analysis.
Results: DPI-treated rats showed significantly reduced numbers of inflammatory cells and production of inflammatory cytokines in BALF compared to LPS-treated rats. In lung tissues, NF-κB and MPO activity, ALI scores, and iNOS expression were significantly decreased in DPI-treated rats compared to LPS-treated rats. Western blot analysis demonstrated that DPI significantly suppressed LPS-induced activation of MAPK and NF-κB pathways.
Conclusion: Our results suggest that DPI may have an anti-inflammatory effect on LPS-induced ALI via suppression of the activation of MAPK and NF-κB pathways. DPI could be a useful therapeutic agent of ALI treatment.
- Copyright ©ERS 2015
