The cigarette smoke component acrolein inhibits expression of the innate immune components IL-8 and human beta-defensin 2 by sinonasal epithelial cells.
BACKGROUND
Tobacco use is associated with poorer outcomes of medical and surgical therapy for chronic rhinosinusitis (CRS), although the underlying mechanism is unknown. Acrolein (AC) is a major component of cigarette smoke that has been shown to suppress innate immune gene expression by human bronchial epithelial cells and murine macrophages. In this study, we explore whether exposure of human sinonasal epithelial cells (HSNECs) to AC similarly reduces their innate immune gene expression.


METHODS
Primary HSNECs from CRS patients were grown in culture, either differentiated or submerged. HSNECs were treated for 30 minutes with 0-50 microM of AC and were subsequently analyzed by real-time polymerase chain reaction and ELISA to determine IL-8 and human beta-defensin (HBD) 2 expression. Total glutathione was measured to see the oxidative stress within the treatment range.


RESULTS
In primary HSNEC, IL-8 mRNA levels decreased dose dependently in the range of 10-50 microM of AC with an eightfold decrease at 50 microM. In addition, a 125-fold decrease at 50 microM for IL-8 protein was observed. HBD-2 mRNA decreased twofold and HBD-2 protein decreased fourfold at 50 microM of AC in primary HSNEC. However, differentiated HSNEC showed a marginal decrease in a dose-dependent manner for both IL-8 and HBD-2 within the range of 10-50 microM of AC. There was no oxidative stress observed over this range of AC concentration.


CONCLUSIONS
The tobacco smoke component AC has the capacity to suppress the inflammatory and innate immune function of sinonasal epithelial cells. Whether this effect contributes to the negative clinical impact of smoking on CRS outcomes merits additional investigation.
Lee
Won Kyung
WK
Department of Otolaryngology-Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-0910, USA.
Ramanathan
Murugappan
M
Spannhake
Ernst W
EW
Lane
Andrew P
AP
D000171:Acrolein / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000378:metabolism*; D009666:Nose / Q000166:cytology*; D010256:Paranasal Sinuses / Q000166:cytology*; D012906:Smoke / Q000032:analysis*; D023083:beta-Defensins / Q000378:metabolism*; D014026:Nicotiana
C106641:DEFB4A protein, human; D016209:Interleukin-8; D012906:Smoke; D023083:beta-Defensins; D000171:Acrolein