[Sitagliptin Inhibits Lipopolysaccharide-induced Inflammatory Response in Human Gingival Fibroblasts by Blocking Nuclear Factor-κB Signaling Pathway]

Overview

Journal Hua Xi Kou Qiang Yi Xue Za Zhi

Specialty Dentistry

Date 2021 Apr 9

PMID 33834669

Citations 1

Authors

Xiang Liu

Wen-Yan Kang

Ling-Ling Shang

Shao-Hua Ge

Affiliations

Soon will be listed here.

Abstract

Objectives: This study was performed to clarify the effects of sitagliptin on -lipopolysaccharide (LPS)-induced inflammatory response in human gingival fibroblasts (HGFs), explore the molecular mechanism of its roles, and provide a foundation for clinical therapeutics in periodontitis.

Methods: Healthy gingival samples were collected from the donors. HGFs were isolated with enzymic digestion method and identified. The effects of LPS and sitagliptin on cell viability were detected by cell-counting kit-8 (CCK8). The mRNA levels of inflammatory cytokines, namely, interleukin (IL)-6, IL-8, C-C motif ligand 2 (CCL2), and superoxide dismutase 2 (SOD2), were evaluated by quantity real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immune sorbent assay (ELISA) was used to measure the secretion protein levels of IL-6, IL-8, and CCL2. Western blot analysis was used to further investigate the activation of nuclear factor (NF)-κB signaling pathway. The effect of NF-κB pathway inhibitor BAY11-7082 on LPS-induced HGF inflammatory cytokines at the gene level was verified by qRT-PCR.

Results: Low concentrations of sitagliptin (0.1, 0.25, and 0.5 µmol·L) did not affect HGF growth in 24 and 48 h, whereas high concentrations of sitagliptin (5-1 000 µmol·L) significantly inhibited cell proliferation. Sitagliptin suppressed 5 µg·mL of LPS-induced IL-6, IL-8, CCL2, and SOD2 gene expression levels in HGF in a concentration-dependent manner. Furthermore, sitagliptin significantly decreased the elevated secretion of IL-6, IL-8, and CCL2 protein induced by LPS. Western blot analysis showed that 0.5 µmol·L of sitagliptin significantly inhibited LPS-induced NF-κB signaling pathway activation. Results of qRT-PCR analysis indicated that 0.5 µmol·L of sitagliptin and 5 µmol·L of BAY11-7082 significantly inhibited LPS-induced IL-6, IL-8, CCL2, and SOD2 gene expressions.

Conclusions: Sitagliptin could significantly inhibit LPS-induced HGF inflammatory response by blocking the NF-κB signaling pathway activation.

Citing Articles

Effects of sitagliptin activation of the stromal cell-derived factor-1/CXC chemokine receptor 4 signaling pathway on the proliferation, apoptosis, inflammation, and osteogenic differentiation of human periodontal ligament stem cells induced by....

Tang X, Zhou Z, Li Q, Jiang D Hua Xi Kou Qiang Yi Xue Za Zhi. 2024; 42(1):37-45.

PMID: 38475949 PMC: 10965348. DOI: 10.7518/hxkq.2024.2023213.

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