Oral squamous cell carcinoma (OSCC) is a usual oral cancer. Therefore, it's essential to identify targets for its early diagnosis and therapy. This research aimed to explore the roles of human β-defensin-3 (hBD-3) and nuclear factor-kappa B (NF-κB) p65 in the pathogenesis and progression of OSCC. The connection between NF-κB p65 and the carcinogenesis of oral cancer was analyzed by immunohistochemical staining. The relative expressions of hBD-3 and NF-κB p65 in OSCC cells were evaluated by qRT-PCR and Western blot. Afterward, hBD-3 was knocked down, and NF-κB p65 was overexpressed. The cell viability and invasion were tested via CCK-8 and Transwell experiment, and the expression of hBD-3, NF-κB p65, and its downstream molecules was evaluated by Western blot. The expression of NF-κB p65 was increased with the aggravation of the oral submucosal fibrosis. HBD-3 and NF-κB p65 were high-expressed in OSCC cells. The viability and invasion abilities of OSCC cells that knocked down hBD-3 were markedly decreased, while they were restored by the overexpression of NF-κB p65. The expressions of NF-κB p65 and c-myc were diminished while IκB and p21 were raised with the knockdown of hBD-3. After overexpression of NF-κB p65, the expression of hBD-3 and IκB did not change markedly, while c-myc was increased and p21 was decreased dramatically. HBD-3 and NF-κB p65 facilitate the proliferation and invasion of OSCC cells, and hBD-3 may promote this process by governing the expression of NF-κB p65 and its downstream c-myc and p21.
Hong Zhou,Xi Tan,Guozhong Chen,Xinxin Liu,Aiping Feng,Zhi Liu,Wei Liu
Atopic dermatitis (AD) is a chronic inflammatory cutaneous disorder in which the skin is affected by microbial dysbiosis . The role of commensal skin microbiota in AD is of great interest. Extracellular vesicles (EVs) are important regulators of skin homeostasis and pathology. The mechanism of preventing AD pathogenesis through commensal skin microbiota–derived EVs remains poorly understood. In this study, we investigated the role of commensal skin bacterium Staphylococcus epidermidis– derived EVs (SE-EVs). We showed that SE-EVs significantly decreased the expression of proinflammatory genes ( TNFα , IL1β , IL6 , IL8 , and iNOS ) through lipoteichoic acid and increased the proliferation and migration of calcipotriene (MC903)-treated HaCaT cells. Furthermore, SE-EVs increased the expression of human β-defensins 2 and 3 in MC903-treated HaCaT cells through toll-like receptor 2, enhancing resistance to S. aureus growth. In addition, topical SE-EV application remarkably attenuated inflammatory cell infiltration (CD4 + T cells and Gr1 + cells), T helper 2 cytokine gene expression ( Il4 , Il13 , and Tlsp ), and IgE levels in MC903-induced AD-like dermatitis mice. Intriguingly, SE-EVs induced IL-17A + CD8 + T-cell accumulation in the epidermis, which may represent heterologous protection. Taken together, our findings showed that SE-EVs reduced AD-like skin inflammation in mice and may potentially be a bioactive nanocarrier for the treatment of AD.
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