Inhibition of apoptotic signals in overgrowth of human gingival fibroblasts by cyclosporin A treatment

Gingival overgrowth is a common side-effect of administration of the immunosuppressant cyclosporin A and the anti-epileptic drug phenytoin. While cyclosporin-induced gingival overgrowth is often accompanied by gingival inflammation, phenytoin-induced gingival overgrowth usually forms fibrotic lesions. To determine whether these drugs alter the inflammatory responses of gingival fibroblasts, we investigated the effects of cyclosporin and phenytoin on Toll-like receptor (TLR)-mediated responses to microbial components. In Chinese hamster ovary reporter cell lines, cyclosporin alone triggered signaling, whereas phenytoin down-regulated signaling induced by the TLR2 or TLR4 ligand. In human gingival fibroblasts, cyclosporin alone did not induce evident inflammatory responses, but augmented the expression of CD54 and the production of interleukin (IL)-6 and IL-8 induced by TLR ligands, whereas phenytoin attenuated those responses. Cyclosporin also augmented CD54 expression in gingiva of mice injected with lipopolysaccharide. These results indicated that cyclosporin positively and phenytoin negatively modulated inflammatory responses of human gingival fibroblasts.

Download Full-text

Cyclosporin A suppresses Porphyromonas gingivalis lipopolysaccharide induced matrix metalloproteinases activities in the co-culture of human gingival fibroblasts and monocyte cell line THP-1

Growth Factors ◽

10.1080/08977194.2020.1755280 ◽

2020 ◽

Vol 38 (2) ◽

pp. 65-74

Author(s):

Lei Jiang ◽

Min Ni Liu ◽

Guo Dong Wang ◽

Qun Wu ◽

Yun Fu Zhao

Keyword(s):

Matrix Metalloproteinases ◽

Cyclosporin A ◽

Cell Line ◽

Porphyromonas Gingivalis ◽

Human Gingival Fibroblasts ◽

Gingival Fibroblasts ◽

Porphyromonas Gingivalis Lipopolysaccharide ◽

Monocyte Cell

Download Full-text

Cyclosporin A and hydroxycyclosporine (M-17) affect the secretory phenotype of human gingival fibroblasts

Journal of Oral Pathology and Medicine ◽

10.1111/j.1600-0714.1998.tb01953.x ◽

2007 ◽

Vol 27 (6) ◽

pp. 260-266 ◽

Cited By ~ 14

Author(s):

Angelo Mariotti ◽

Thomas Hassell ◽

David Jacobs ◽

C. Jo Manning ◽

Arthur F. Hefti

Keyword(s):

Cyclosporin A ◽

Human Gingival Fibroblasts ◽

Gingival Fibroblasts ◽

Secretory Phenotype

Download Full-text

Cyclosporin A Affects Signaling Events Differentially in Human Gingival Fibroblasts

Journal of Dental Research ◽

10.1177/154405910508400609 ◽

2005 ◽

Vol 84 (6) ◽

pp. 532-536 ◽

Cited By ~ 16

Author(s):

A. Bostrom ◽

H. Bharath ◽

A. Saulewicz ◽

A.S. Narayanan

Keyword(s):

Transcription Factors ◽

Cyclosporin A ◽

Map Kinases ◽

Cell Types ◽

Binding Activity ◽

Human Gingival Fibroblasts ◽

Common Side Effect ◽

Gingival Fibroblasts ◽

Calcium Blockers ◽

Gingival Overgrowth

Gingival overgrowth is a common side-effect of the administration of cyclosporin A (CSA), phenytoin, and calcium blockers. To identify the signaling mechanisms possibly involved in the overgrowth, we examined how CSA affects the activities of MAP kinases and transcription factors in human gingival fibroblasts (HGF). The HGF were treated with CSA and TNF-α or PDGF. DNA-binding activity of NFAT, NFκB, and AP-1 transcription factors was determined by gel shift assay, and JNK, p38, and ERK1 and ERK2 activation was assessed by Western blot analysis of immunoprecipitates. The CSA inhibited NFAT, NFκB, and p38 and JNK activities; however, ERK1 and ERK2 were not affected significantly. AP-1 activity increased ~ 4.5-fold. Our results indicate that CSA affects signaling molecules in HGF differently from other cell types, and that a CSA-induced increase in AP-1 activity may affect the expression of fibrogenic molecules in gingiva and promote gingival overgrowth.

Download Full-text