ABSTRACT
Aquaporin 3 (AQP3) is the predominant water channel protein in human keratinocytes and acts as an inflammatory mediator in some lesions. A chronic, inflammatory process of periodontitis is related with a dramatic change of surrounding fluid homeostasis to plasma extravasation. The exact pattern of aquaporin (AQP) water channel expression and its mechanism in periodontal disease is still unknown. We describe herein an up-regulated AQP3 expression in the epithelial lesion with chronic periodontitis and its functional role. The levels of AQP3 expression in inflamed gingival epithelial tissues were significantly higher than those of healthy subjects. Consistent with these results, AQP3 expression (i.e., levels of mRNA and protein) in cultured rat primary gingival epithelial cells and the human gingival epithelial cell line Ca9-22 were strongly increased in response to TNF-alpha treatment through the 55 kDa TNF-alpha receptor (TNFR I). In this context, small interfering RNA- (siRNA)-mediated "aqp-3 gene silencing," which could reduce AQP3 expression by more than 65%, significantly attenuated selected proinflammatory events of ICAM-1 expression induced by TNF-alpha in Ca9-22. A sixfold increase in leukocyte adherence to TNF-alpha-stimulated epithelial cells was demonstrated by an adherence assay (P < 0.001) and pretreatment with AQP3 siRNA and anti-ICAM-1 antibody reduced leukocyte retention by 85% (P < 0.001). Our study indicates for the first time a novel important mode in the regulation of the inflammatory response through TNF-alpha/TNFR I ligation at the site of epithelial lesions by specialized membrane channel AQP3 and ICAM-1 protein, which is closely implicated in the development of periodontitis mechanisms.
Subject(s)
Aquaporin 3/metabolism , Epithelial Cells/metabolism , Gingiva/metabolism , Periodontitis/metabolism , Tumor Necrosis Factor-alpha/metabolism , Animals , Aquaporin 3/genetics , Cell Adhesion , Cell Line , Chronic Disease , Epithelial Cells/immunology , Female , Gingiva/immunology , Humans , Intercellular Adhesion Molecule-1/metabolism , Leukocytes/metabolism , Male , Middle Aged , Periodontitis/immunology , RNA Interference , RNA, Messenger/metabolism , RNA, Small Interfering/metabolism , Rats , Receptors, Tumor Necrosis Factor, Type I/metabolism , Recombinant Proteins/metabolism , Time Factors , Transfection , Up-RegulationABSTRACT
Oral candidiasis is the symptomatic development of superficial infection with many forms of clinical manifestation. The treatment of choice should include the antifungal agents which act topically in the oral cavity so that the systematic adverse effects are minimal. They should have good impregnation to the oral mucosa and prolonged effect. In patients with chronic or recurrent infection or being immunological compromised, successful treatment can be achieved by increased dosage and extended duration of antifungal therapy.
