biomedicines Article Lobeglitazone Exerts Anti-Inflammatory Effect in Lipopolysaccharide-Induced Bone-Marrow Derived Macrophages Dabin Jeong 1,2 , Wan-Kyu Ko 1,3 , Seong-Jun Kim 1,3 , Gong-Ho Han 1,3 , Daye Lee 1,3 , Seung-Hun Sheen 1, * and Seil Sohn 1, *   Citation: Jeong, D.; Ko, W.-K.; Kim, S.-J.; Han, G.-H.; Lee, D.; Sheen, S.-H.; Sohn, S. Lobeglitazone Exerts Anti-Inflammatory Effect in Lipopolysaccharide-Induced Bone-Marrow Derived Macrophages. Biomedicines 2021, 9, 1432. https:// doi.org/10.3390/biomedicines9101432 Academic Editor: Alexander N. Orekhov Received: 30 August 2021 Accepted: 7 October 2021 Published: 10 October 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Department of Neurosurgery, CHA Bundang Medical Center, Seongnam-si 13496, Korea; dbjekqls77@gmail.com (D.J.); wankyu@chauniv.ac.kr (W.-K.K.); ksj987456@chauniv.ac.kr (S.-J.K.); hgh429@chauniv.ac.kr (G.-H.H.); day03@chauniv.ac.kr (D.L.) 2 Department of Biology, Lawrence University, Appleton, WI 54911, USA 3 Department of Biomedical Science, CHA University, Seongnam-si 13493, Korea * Correspondence: nssheen@cha.ac.kr (S.-H.S.); sisohn@cha.ac.kr (S.S.) 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. Keywords: bone-marrow derived macrophages; lipopolysaccharide; lobeglitazone; anti-inflammation; mitogen-activated protein kinase 1. 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 in- flammation. 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) [2–7]. Upregulation of macrophage inflammation is characterized by aberrant increase of pro-inflammatory mediators. Indeed, accumulation of aforementioned pro-inflammatory molecules is implicated in pathogenesis of autoimmune and inflammatory diseases such as type 2 diabetes, atherosclerosis, and spinal cord injury [8–10]. Current pharmaceutical interventions including use of corticosteroid and non-steroidal anti-inflammatory drugs (NSAIDs) are commonly practiced for managing inflammation [11,12]. However, 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]. Biomedicines 2021, 9, 1432. https://doi.org/10.3390/biomedicines9101432 https://www.mdpi.com/journal/biomedicines