Apocynin protects mesangial cells from lipopolysaccharide-induced inflammation by exerting heme oxygenase 1-mediated monocyte chemoattractant protein-1 suppression

Bhatt,Nirmal  Prasad; Park,Jin-Young; Lee,Hee  Jae; Kim,Sung-Soo; Kwon,Yong-Soo; Chun,Wanjoo

doi:10.3892/ijmm.2017.3090

Apocynin protects mesangial cells from lipopolysaccharide-induced inflammation by exerting heme oxygenase 1-mediated monocyte chemoattractant protein-1 suppression

Authors:
- Nirmal Prasad Bhatt
- Jin-Young Park
- Hee Jae Lee
- Sung-Soo Kim
- Yong-Soo Kwon
- Wanjoo Chun
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Affiliations: Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon, Gangwon 200-701, Republic of Korea, College of Pharmacy, Kangwon National University, Chuncheon, Gangwon 200-701, Republic of Korea
Published online on: August 4, 2017 https://doi.org/10.3892/ijmm.2017.3090
Pages: 1294-1301

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Abstract

Renal failure is observed in the pathological progression of sepsis and septic shock. Renal mesangial cells (RMCs) have been implicated in renal failure as a result of producing mediators, such as monocyte chemoattractant protein-1 (MCP-1) in response to lipopolysaccharide (LPS). Mitogen-activated protein kinases (MAPKs) have been demonstrated to mediate the LPS-induced inflammatory response in RMCs. Although previous studies indicated a promising effect of apocynin in various inflammatory conditions, its antiseptic efficacy in mesangial cells remains to be clearly determined. In the present study, the anti-inflammatory effects of apocynin and its underlying mechanism were examined in LPS-challenged RMCs. Apocynin significantly inhibited nitric oxide (NO) production in LPS-challenged RMCs and the expression levels of inducible NO synthase and cyclooxygenase-2. In addition, the level of LPS-induced MCP-1 expression was significantly attenuated with apocynin. Furthermore, apocynin significantly suppressed the activation of MAPKs, such as extracellular signal-regulated kinases 1/2 and p38, but not c-Jun N-terminal kinases. Apocynin exhibited significantly increased expression of heme oxygenase-1 (HO-1) induction via nuclear factor (erythroid-derived 2)-like-2 (Nrf-2) phosphorylation. Inhibition of HO-1 with zinc protoporphyrin significantly abolished apocynin-induced suppression of MCP-1, indicating that HO-1 is significant in the suppression of MCP-1. Thus, apocynin exerts antiseptic activity via the suppression of pro-inflammatory signaling pathways and the activation of cytoprotective signaling pathways, such as HO-1/Nrf-2 in RMCs, indicating that apocynin may present as a promising candidate for in vivo evaluation of a therapeutic agent for inflammation-associated renal disorders.

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