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- Title
The upregulation of cystatin C in human gingival fibroblasts stimulated with cyclosporine A.
- Authors
Tsai, C.‐H.; Yang, S.‐F.; Huang, F.‐M.; Chang, Y.‐C.
- Abstract
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.
- Subjects
CYSTATINS; CYCLOSPORINE; IMMUNOHISTOCHEMISTRY; POLYMERASE chain reaction; INTERLEUKIN-1; CYTOKINES
- Publication
Journal of Periodontal Research, 2009, Vol 44, Issue 4, p459
- ISSN
0022-3484
- Publication type
Article
- DOI
10.1111/j.1600-0765.2008.01147.x