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Lobeglitazone Exerts Anti-Inflammatory Effect in Lipopolysaccharide-Induced Bone-Marrow Derived Macrophages
Dabin Jeong1,2, Wan-Kyu Ko1,3, Seong-Jun Kim1,3
1Department of Neurosurgery, CHA Bundang Medical Center, Seongnam-si 13496, Korea.
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.
Insights
Lobeglitazone (LOBE) reduces inflammation in macrophages by decreasing nitric oxide and pro-inflammatory gene expression. This anti-inflammatory effect may involve the inhibition of the mitogen-activated protein kinase (MAPK) signaling pathway.
Area of Science:
- Immunology
- Pharmacology
Background:
- Inflammation is a key process in many diseases.
- Macrophages play a central role in inflammatory responses.
- Lipopolysaccharide (LPS) is a potent inducer of inflammation in macrophages.
Purpose of the Study:
- To investigate the anti-inflammatory effects of lobeglitazone (LOBE).
- To determine LOBE's impact on LPS-induced inflammation in bone-marrow derived macrophages (BMDMs).
Main Methods:
- LPS was used to induce inflammation in BMDMs.
- Nitric oxide (NO) production was quantified.
- Pro-inflammatory gene expression was measured using RT-qPCR.
- Mitogen-activated protein kinase (MAPK) pathway activation was assessed via Western blot analysis of ERK and JNK phosphorylation.
Main Results:
- LOBE significantly reduced LPS-induced NO production.
- LOBE suppressed the expression of key pro-inflammatory genes (IL-1β, IL-6, iNOS, COX-2, MCP-1).
- LOBE decreased the phosphorylation of ERK and JNK proteins in the MAPK signaling pathway.
Conclusions:
- Lobeglitazone exhibits significant anti-inflammatory properties in LPS-stimulated BMDMs.
- LOBE effectively reduces NO production and pro-inflammatory mediator expression.
- The anti-inflammatory mechanism of LOBE may involve the inhibition of the MAPK signaling pathway.
