Lobeglitazone Exerts Anti-Inflammatory Effect in Lipopolysaccharide-Induced Bone-Marrow Derived Macrophages.

Dabin Jeong,Seung-Hun Sheen,Daye Lee,Gong-Ho Han,Seil Sohn,Wan-Kyu Ko,Seong-Jun Kim

doi:10.3390/biomedicines9101432

Dabin Jeong, Seung-Hun Sheen + Show 5 more

Open Access

https://doi.org/10.3390/biomedicines9101432

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Abstract

The purpose of this study is to elucidate the anti-inflammatory effect of lobeglitazone (LOBE) in lipopolysaccharide (LPS)-induced bone-marrow derived macrophages (BMDMs). We induced nitric oxide (NO) production and pro-inflammatory gene expression through LPS treatment in BMDMs. The changes of NO release and expression of pro-inflammatory mediators by LOBE were assessed via NO quantification assay and a real-time quantitative polymerase chain reaction (RT-qPCR), respectively. In addition, the regulatory effect of LOBE on activation of mitogen-activated protein kinase (MAPK) signaling pathway was investigated by measuring the phosphorylation state of extracellular regulatory protein (ERK) and c-Jun N-terminal kinase (JNK) proteins by Western blot. Our results show that LOBE significantly reduced LPS-induced NO production and pro-inflammatory gene expression of interleukin-1β (IL-1β), IL-6, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and monocyte chemoattractant protein-1 (MCP-1). Moreover, LOBE reduced phosphorylation levels of ERK and JNK of MAPK signaling pathway. In conclusion, LOBE exerts an anti-inflammatory effect in LPS-induced BMDMs by suppression of NO production and pro-inflammatory gene expression, and this effect is potentially through inhibition of the MARK signaling pathway.

Highlights

Our results demonstrate that LOBE down-regulated key pro-inflammatory mediators at transcription level, potentially through inhibition of extracellular regulatory protein (ERK) and c-Jun N-terminal kinase (JNK) signaling of mitogen-activated protein kinase (MAPK) pathway
LOBE doses ranging from 1 μM to 200 μM did not significantly drug cytotoxicity affecting investigation of the anti-inflammatory effect, the cytotoxicity increase nor decrease cell viability
nitric oxide (NO) is produced by a number of distinct sets of NO synthases in in macrophages, of which expression of inducible nitric oxide synthase (iNOS) is notable in the context of inflammation macrophages, of which expression of iNOS is notable in the context of inflammation [2]

Summary

Introduction

Inflammation is the host’s defensive response against pathogenic infection, cellular stress, and tissue injury [1], and macrophages are critical players in modulation of inflammation. They survey pathogen invasion and respond to cellular stress by releasing a variety of pro-inflammatory mediators such as nitric oxide (NO), interleukin-1β (IL-1β), IL-6, cyclooxygenase-2 (COX-2), and monocyte chemoattractant protein-1 (MCP-1) [2,3,4,5,6,7]. Upregulation of macrophage inflammation is characterized by aberrant increase of pro-inflammatory mediators. Current pharmaceutical interventions including use of corticosteroid and non-steroidal anti-inflammatory drugs (NSAIDs) are commonly practiced for managing inflammation [11,12]. Off-target events and adverse side effects of current anti-inflammatory drug imply unmet demand for identification of a new drug with potential anti-inflammatory properties [13]

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