Cigarette smoke exposure is associated with vitamin D3 deficiencies in patients with chronic rhinosinusitis.
BACKGROUND
Cigarette smoke (CS) plays a role in the exacerbation of chronic rhinosinusitis (CRS); however, the mechanism for this is unknown. We hypothesize that CS impairs human sinonasal epithelial cell (HSNEC) conversion of 25(OH)D3 (25VD3) to 1,25-dihydroxyvitamin D3 (1,25VD3) and, furthermore, that supplementation with 1,25VD3 will reverse smoke-induced inflammatory responses by HSNECs.


OBJECTIVE
We sought to determine the effect of CS on vitamin D3 (VD3) levels, conversion, and regulation of CS-induced inflammation in control subjects and patients with CRS.


METHODS
Blood and sinus tissue explants were collected at the time of surgery from control subjects, patients with chronic rhinosinusitis without nasal polyps, and patients with chronic sinusitis with nasal polyps (CRSwNP). Expression of VD3 metabolizing enzymes were measured by using RT-PCR. Primary HSNECs were cultured from tissue explants. 25VD3 with and without cigarette smoke extract (CSE) was used to examine conversion of 25VD3 to 1,25VD3, as well as HSNEC production of proinflammatory cytokines.


RESULTS
CS exposure was associated with reduced circulating and sinonasal 25VD3 levels in all groups compared with those seen in CS-naive, disease-matched counterparts. CS exposure decreased expression of CYP27B1 and was especially pronounced in patients with CRSwNP. CSE impairs control HSNEC conversion of 25VD3. HSNECs from patients with CRSwNP also demonstrate an intrinsic reduction in conversion of 25VD3 to 1,25VD3. Exogenous 1,25VD3 reduces CSE-induced cytokine production by HSNECs.


CONCLUSIONS
Exposure to CS is associated with reduced 25VD3 levels and an impaired ability of HSNECs to convert 25VD3 to 1,25VD3. Addition of 1,25VD3 reduces the proinflammatory effects of CS on HSNECs. Impaired VD3 conversion by CS exposure represents a novel mechanism through which CS induces its proinflammatory effects.
Department of Otolaryngology-Head & Neck Surgery, Medical University of South Carolina, Charleston, SC; Department of Pediatrics, Medical University of South Carolina, Charleston, SC; Ralph H. Johnson VA Medical Center, Charleston, SC. Electronic address: konopa@musc.edu.
Jennifer K
JK
Mulligan
Department of Otolaryngology-Head & Neck Surgery, Medical University of South Carolina, Charleston, SC.
Whitney
W
Nagel
Department of Otolaryngology-Head & Neck Surgery, Medical University of South Carolina, Charleston, SC.
Brendan P
BP
O'Connell
Department of Otolaryngology-Head & Neck Surgery, Medical University of South Carolina, Charleston, SC.
Jennifer
J
Wentzel
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC.
Carl
C
Atkinson
Department of Otolaryngology-Head & Neck Surgery, Medical University of South Carolina, Charleston, SC; Ralph H. Johnson VA Medical Center, Charleston, SC.
Rodney J
RJ
Schlosser
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D002112:Calcifediol / Q000378:metabolism; D002117:Calcitriol / Q000172:deficiency* / Q000494:pharmacology; D016022:Case-Control Studies; D002908:Chronic Disease; D045424:Complex Mixtures / Q000302:isolation & purification / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000150:complications / Q000378:metabolism / Q000473:pathology; D061251:Primary Cell Culture; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012220:Rhinitis / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D012852:Sinusitis / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D012906:Smoke; D014026:Nicotiana / Q000737:chemistry*; D014808:Vitamin D Deficiency / Q000150:complications / Q000378:metabolism* / Q000473:pathology
D045424:Complex Mixtures; D012906:Smoke; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol; D002112:Calcifediol
Vitamin D; epithelial cell; secondhand smoke; sinusitis