ABSTRACT
The aryl hydrocarbon receptor nuclear translocator (ARNT) is a transcription factor associated with adaptive responses to cellular stress. Its role in cutaneous squamous cell carcinoma (cSCC) remains poorly understood. The aim of this study was to investigate the role of ARNT in cSCC. Immunohistochemistry revealed downregulation of ARNT in cSCC, precancerous lesions (actinic keratosis), and cells. Knockdown of ARNT in A431 and SCL-1 cells significantly enhanced cell growth and metastasis. Microarray analysis and Ingenuity Pathway Analysis confirmed that loss of ARNT in A431 cells was highly correlated with cell growth and movement and upregulated CXCL3 expression. Cellular and xenograft experiments further confirmed that ARNT regulates cSCC proliferation and invasiveness in a CXCL3-dependent manner. ARNT may regulate CXCL3 expression through ROS-STAT3 pathway. In conclusion, this study demonstrates that ARNT plays a critical role in the development of cSCC and significantly affects the proliferation and metastatic ability of cSCC cells. It has the potential to serve as an ideal treatment target for cSCC.
ABSTRACT
UNLABELLED: Pemphigus is a complex dermatologic autoimmune bullous disease whose pathogenic mechanism is not fully understood. Anti-desmoglein-1 (Dsg1) and anti- Dsg3 autoantibodies play an important role in the pathogenesis of pemphigus. OBJECTIVES: To investigate the role of T-helper17 (Th17) and regulatory T (Treg) cells in the pathogenesis of pemphigus in fifty-one patients and twenty-six healthy individuals (control group). METHODS: Levels of CD3(+)CD8(-) IL-17 expressing Th cells and CD4(+)CD25(hi)Foxp3(+) Treg cells were determined by FACS in both groups, along with anti-Dsg1 and Dsg3 antibody titers. An analysis of the correlation between Th17 and Treg cells was performed. RESULTS: Th17 cell numbers were significantly higher in pemphigus patients than in normal controls (P = 0.014), especially in the acute onset and chronic active stages (P = 0.004 and 0.022). Conversely, Treg cells in pemphigus patients were significantly fewer than in the control group (P<0.001). The same trend was observed between the acute onset and the remittent stage patients (P = 0.006). We found a negative correlation between Th17 and Treg cell populations (r = -0.532, P<0.001). Anti-Dsg1 and Dsg3 antibody titers were higher in patients in the active stage than in the remittent stage, with an increased IgG4/IgG1 subclass ratio. There was no statistically significant correlation between Th17/Treg ratios and anti-Dsg1 or Dsg3 antibody titers. CONCLUSION: These findings show an imbalance of Th17 and Treg cell populations in pemphigus patients, which might result in the activation and proliferation of effector T cells, further up-regulating B cell activity and antibody production.