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The upregulation of cystatin C in human gingival fibroblasts stimulated with cyclosporine A
Author(s) -
Tsai C.H.,
Yang S.F.,
Huang F.M.,
Chang Y.C.
Publication year - 2009
Publication title -
journal of periodontal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.31
H-Index - 83
eISSN - 1600-0765
pISSN - 0022-3484
DOI - 10.1111/j.1600-0765.2008.01147.x
Subject(s) - cystatin c , cystatin , porphyromonas gingivalis , proinflammatory cytokine , aggregatibacter actinomycetemcomitans , immunohistochemistry , downregulation and upregulation , staining , fibroblast , tumor necrosis factor alpha , periodontitis , medicine , pathology , chemistry , inflammation , biology , cell culture , creatinine , biochemistry , gene , genetics
Background and Objective: Cystatin C is a 13 kDa non‐glycosylated, basic protein belonging to the cystatin family. It is consistently and dramatically upregulated in a variety of fibrotic diseases. However, little is known about the correlation between cystatin C and cyclosporine A‐induced gingival overgrowth. The aim of this study was to compare cystatin C expression in normal, healthy gingival tissues and cyclosporine A‐induced gingival overgrowth specimens and further explore the potential mechanism that may result in cystatin C expression. Material and Methods: Fifteen cyclosporine A‐induced gingival overgrowth specimens and five normal gingival tissues were examined by immunohistochemistry. Three human gingival fibroblast (HGF) strains were established from crown‐lengthening surgery. The reverse transcriptase‐polymerase chain reaction was used to investigate the effects on HGFs exposed to cyclosporine A. In addition, predominant periodontal pathogens ( Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis ) and proinflammatory cytokines (interleukin‐1α and tumor necrosis factor‐α) were added to seek the possible regulatory mechanisms of cystatin C expression. Results: The cystatin C staining in gingival tissue was stronger in the cyclosporine A‐induced gingival overgrowth group than in the normal gingival group ( p < 0.05). Intensive staining for cystatin C expression was observed mainly in the cytoplasm of fibroblasts, epithelial cells and inflammatory cells. Moreover, cystatin C expression was significantly higher in cyclosporine A‐induced gingival overgrowth specimens with higher levels of inflammatory infiltrates ( p < 0.05). A concentration of 200 ng/mL cyclosporine A was found to increase cystatin C expression in HGFs in a time‐dependent manner ( p < 0.05). The addition of periodontal pathogens and proinflammatory cytokines significantly increased the expression of cystatin C compared with cyclosporine A alone ( p < 0.05). Conclusion: The increased ability of protein accumulation by cystatin C is one of several factors mediating cyclosporine A‐induced gingival overgrowth. In addition, cyclosporine A may predispose to gingival overgrowth in inflammatory environments.