Glucocorticoids suppress NF-kappaB activation induced by LPS and PGN in paranasal sinus epithelial cells.

Objectives: The aim of this study was to examine the innate immune response induced by toll- like receptors (TLRs) in the paranasal sinus epithelial cells in cell culture models and to exam- ine the effect of glucocorticoids (GCs) on the innate immune response. Methods:After stimulation with lipopolysaccharide (LPS) and peptidoglycan (PGN), p50 level was measured as an index of the innate response in the paranasal sinus epithelium. To observe the effect of GCs, the specimens were pre-treated with dexamethasone (DEX) for 48 hours prior to stimulation. On immunocytochemistry GR, TLR2 and TLR4 in the paranasal sinus epitheli- um were observed. Results:The p50 activity levels increased after stimulation with LPS and PGN in a dose-depen- dent manner. Pretreatment with DEX significantly suppressed the increase in p50 activity levels induced by LPS and PGN. On immunocytochemistry, TLR2 and TLR4 immunoreactivities were relatively high after 48h DEX pretreatment. Conclusion:The increase in NF-!B activity after LPS and PGN stimulation suggests that stim- ulation through TLR2 and TLR4 may induce high cytokine expression and inflammatory cell migration in the paranasal sinus epithelial cells. In paranasal sinus epithelial cells GCs not only have anti-inflammatory effects through transcription factor inhibition but also enhance innate host defences. SUMMARY