Glucocorticoids suppress NF-kappaB activation induced by LPS and PGN in paranasal sinus epithelial cells.
OBJECTIVE
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 examine 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 epithelium were observed.


RESULTS
The p50 activity levels increased after stimulation with LPS and PGN in a dose-dependent 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.


CONCLUSIONS
The increase in NF-kappaB activity after LPS and PGN stimulation suggests that stimulation 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.
Nishi
Yasuyuki
Y
Department of Otorhinolaryngology and Head and Neck Surgery, Division of Clinical Medical Science, Programs for Applied Biomedicine, Graduate School of Biomedical Science, Hiroshima University, Minami-ku, Hiroshima, Japan. y-nishi@yg8.so-net.ne.jp
Takeno
Sachio
S
Ishino
Takashi
T
Hirakawa
Katsuhiro
K
D000328:Adult; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000276:immunology*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007113:Immunity, Innate; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D016328:NF-kappa B / Q000032:analysis / Q000187:drug effects*; D010256:Paranasal Sinuses / Q000276:immunology*; D010457:Peptidoglycan / Q000494:pharmacology; D051195:Toll-Like Receptor 2 / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000502:physiology*
D005938:Glucocorticoids; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010457:Peptidoglycan; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D003907:Dexamethasone