Estrogen reinforces barrier formation and protects against tumor necrosis factor alpha-induced barrier dysfunction in oral epithelial cells

PURPOSE: Epithelial barrier dysfunction is involved in the pathophysiology of periodontitis and oral lichen planus. Estrogens have been shown to enhance the physical barrier function of intestinal and esophageal epithelia, and we aimed to investigate the effect of estradiol (E2) on the regulation of physical barrier and tight junction (TJ) proteins in human oral epithelial cell monolayers. METHODS: HOK-16B cell monolayers cultured on transwells were treated with E2, an estrogen receptor (ER) antagonist (ICI 182,780), tumor necrosis factor alpha (TNFα), or dexamethasone (Dexa), and the transepithelial electrical resistance (TER) was then measured. Cell proliferation was measured by the cell counting kit (CCK)-8 assay. The levels of TJ proteins and nuclear translocation of nuclear factor (NF)-κB were examined by confocal microscopy. RESULTS: E2 treatment increased the TER and the levels of junctional adhesion molecule (JAM)-A and zonula occludens (ZO)-1 in a dose-dependent manner, without affecting cell proliferation during barrier formation. Treatment of the tight-junctioned cell monolayers with TNFα induced decreases in the TER and the levels of ZO-1 and nuclear translocation of NF-κB. These TNFα-induced changes were inhibited by E2, and this effect was completely reversed by co-treatment with ICI 182,780. Furthermore, E2 and Dexa presented an additive effect on the epithelial barrier function. CONCLUSIONS: E2 reinforces the physical barrier of oral epithelial cells through the nuclear ER-dependent upregulation of TJ proteins. The protective effect of E2 on the TNFα-induced impairment of the epithelial barrier and its additive effect with Dexa suggest its potential use to treat oral inflammatory diseases involving epithelial barrier dysfunction.

Study on relation between junctional adhesion molecule family A expression level and radiosensitivity of nasopharyngeal carcinoma cell line / 重庆医学

Objective The radiotherapy resistance is one of important causes for nasopharyngeal carcinoma(NPC) treatment failure.Junctional adhesion molecule A(JAMA)is closely correlated with the tumor poor prognosis.Thus this experiment is to in vestigate the relationship between JAMA expression and the radiosensitivity of NPC.Methods To overexpress or interfere the JAMA expression in CNE2 and HONE1 cell lines.Then different doses of X-ray were adopted to conduct irradiation.The cell clone formation capacity and cellular apoptosis change were detected after 24 h.The role of JAMA in the NPC radiotherapy was understand.The related signal pathway protein in cell lines with different JAMA expression was detected by Western blot.Results The cell lines with low JAMA expression were more sensitive to radiotherapy:After low JAMA expression,the D0 value in the CNE2 cell line was decreased from 3.26 ±0.78 to 1.92 ± 0.23;the Dq value was decreased from 46.51 ± 4.27 to 32.12 ± 3.19.The radio therapy induced apoptosis was significantly increased in the cell lines with low JAMA expression,after low JAMA expressing,thcellular apoptosis was elevated from 6.9 ％ ± 0.9 ％ to 13.7 ％ ± 1.3 ％;the HONE1 cellular apoptosis was elevated from 6.5 ％ + 1.1 ％ to 12.3 ％ ± 1.7％;JAMA overexpression cell lines were significantly decreased.The preliminary mechanism research results showed that JAMA played the effect via Akt signal pathway.Conclusion This research results verifiy that JAMA expression level is closely correlated with the radiosensitivity of NPC cell line:JAMA can increase the radiotherapy resistance of NPC cell lines,which provides a new feasible research direction for NPC enhancing radiosensitivity.