Cigarette smoke upregulates SPRR3 by favoring c-Jun/Fra1 heterodimerization in human bronchial epithelial cells.

AIM: The airway epithelium of smokers exhibits upregulated SPRR3, an indicator of pathogenic keratinization. The mechanisms underlying this phenomenon require investigation.

PATIENTS &

METHODS

Human bronchial epithelial (HBE) SPRR3 expression was analyzed by smoking status. Primary HBE cells were exposed to cigarette smoke (CS). SPRR3 expression, SPRR3 promoter activity, AP-1 factor binding and AP-1 factors' effects were analyzed.

RESULTS

Current smokers display SPRR3 upregulation relative to never smokers. CS upregulates SPRR3 transcription in an exposure-dependent manner. CS promotes c-Jun and Fra1 binding to the SPRR3-AP-1/TRE site. Wild-type c-Jun and Fra1 upregulate, whereas c-Jun and Fra1, dominant-negative mutants, suppress SPRR3 promoter activity.

CONCLUSION

CS induces SPRR3 upregulation in HBE cells by promoting aberrant c-Jun/Fra1 dimerization.