Sitagliptin attenuates inﬂammatory responses in lipopolysaccharide‑stimulated cardiomyocytes via nuclear factor‑κB pathway inhibition

Lin,Chien‑Hung; Lin,Chung‑Ching

doi:10.3892/etm.2016.3255

Sitagliptin attenuates inﬂammatory responses in lipopolysaccharide‑stimulated cardiomyocytes via nuclear factor‑κB pathway inhibition

Authors:
- Chien‑Hung Lin
- Chung‑Ching Lin
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Affiliations: Institute of Clinical Medicine, National Yang‑Ming University, Taipei 11221, Taiwan R.O.C., Seeing Bioscience Co., Ltd., Datong, Taipei 22067, Taiwan R.O.C.
Published online on: April 11, 2016 https://doi.org/10.3892/etm.2016.3255
Pages: 2609-2615

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Abstract

Glucagon‑like peptide‑1 (GLP‑1) and GLP‑1 receptors (GLP‑1Rs) are responsible for glucose homeostasis, and have been shown to reduce inflammation in preclinical studies. The aim of the present study was to determine whether sitagliptin, an inhibitor of the enzyme dipeptidyl peptidase‑4 (DPP‑4), as a GLP‑1 receptor agonist, exerts an anti‑inflammatory effect on cardiomyoblasts during lipopolysaccharide (LPS) stimulation. Exposure to LPS increased the expression levels of tumor necrosis factor (TNF)‑α, interleukin‑6 (IL)‑6 and IL‑1β in H9c2 cells, and also resulted in elevations in cyclooxygenase‑2 (COX‑2) and inducible nitric oxide synthase (iNOS) expression and nuclear factor‑κB (NF‑κB) nuclear translocation. Treatment with the DPP‑4 inhibitor sitagliptin dose‑dependently downregulated the mRNA levels of IL‑6, COX‑2 and iNOS in LPS‑stimulated H9c2 cells. In addition, sitagliptin inhibited the increased protein expression of IL‑6, TNF‑α and IL‑1β. NF‑κB mRNA expression was reduced and its translocation to the nucleus was suppressed by treatment with sitagliptin. The present results demonstrated that sitagliptin exerts a beneficial effect on cardiomyoblasts exposed to LPS by inhibiting expression of inflammatory mediators and suppressing NF‑κB activation. These findings indicate that the DPP‑4 inhibitor sitagliptin may serve a function in cardiac remodeling attributed to sepsis‑induced inflammation.

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