Increase of CD26/Dipeptidyl Peptidase IV Expression on Human Gingival Fibroblasts upon Stimulation with Cytokines and Bacterial Components

Abstract

CD26/dipeptidyl peptidase IV (DPPIV) is a cell surface ectoenzyme which participates in immune and inflammatory reactions. We found that CD26 was only partially expressed on human fibroblasts from periodontal tissues, whereas fibroblasts from lung and skin expressed CD26 constitutively as revealed by flow cytometry. We examined the possible upregulation of CD26 expression on human gingival fibroblasts in response to various stimulants. Interleukin-1α (IL-1α); tumor necrosis factor alpha; gamma interferon; lipopolysaccharide fromPorphyromonas gingivalis, Prevotella intermedia, and Escherichia coli; andPrevotella glycoprotein augmented CD26 expression on gingival fibroblasts. Among the stimulants, IL-1α exhibited the most potent activity. Enzymatic activity of CD26 induced by IL-1α on fibroblasts was determined colorimetrically in terms of Gly-Pro hydrolysis of a synthetic chromogenic substrate, Gly-Prop-nitroanilide. Among various inhibitors tested, diprotin A and phenylmethylsulfonyl fluoride inhibited the enzymatic activity, suggesting that the enzyme induced by IL-1α was DPPIV. The upregulation of CD26 mRNA expression upon stimulation with IL-1α was also revealed by a quantitative reverse transcription-PCR assay. In the kinetic experiment, 48 h and several days were required for maximum CD26 mRNA accumulation and CD26 molecule expression on the cell surface, respectively. The addition of cycloheximide at 2 h before IL-1α stimulation almost completely inhibited the accumulation of CD26 mRNA. These results suggested that induction of CD26 on human gingival fibroblasts is regulated at the transcriptional level and is also dependent on a de novo-synthesized protein factor(s).

DPP4 in Cardiometabolic Disease

“…5 In addition to interleukin (IL)-12 and tumor necrosis factor (TNF)-α, IL-1α has also been shown to regulate the expression of DPP4. 8 The promoter for DPP4 also contains consensus sites for nuclear factor (NF)-κB, SP-1 (specificity protein 1), EGFR (epidermal growth factor receptor), AP-1 factor (activator protein 1), and hepatocyte NF-1. IL-12 enhances the translation but not transcription of DPP4 in activated lymphocytes, whereas TNFα decreases cell surface expression of DPP4, suggesting a regulatory role of IL-12 and TNFα in the translation and translocation of DDP4.…”

Dpp4 inhibition as a therapeutic strategy in cardiometabolic disease: Incretin-dependent and -independent function

“…In contrast, DPP4 expression on natural killer cells is induced by IL-2, IL-12, or IL-15, but not IFN-γ [66]. The expression of DPP4 on gingival fibroblasts is shown to be regulated by IL-1α [67]. A recent study demonstrates that IL-1α also contributes to the upregulation of DPP4 expression on epithelial cells and stromal cells in wounded dermis [68].…”

Dipeptidyl peptidase-4 inhibition: insights from the bench and recent clinical studies

“…IL-12 enhances the translation but not transcription of DPP4 in activated lymphocytes, while TNFα decreases expression of DPP4, suggesting that DPP4 translation and translocation is regulated by cytokines such as IL-12 and TNFα [5]. IL-1α has also been shown to upregulates the expression of DPP4 [6,7].…”