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
  • View Affiliations

  • 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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October-2017
Volume 40 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Bhatt NP, Park J, Lee HJ, Kim S, Kwon Y and Chun W: Apocynin protects mesangial cells from lipopolysaccharide-induced inflammation by exerting heme oxygenase 1-mediated monocyte chemoattractant protein-1 suppression. Int J Mol Med 40: 1294-1301, 2017
APA
Bhatt, N.P., Park, J., Lee, H.J., Kim, S., Kwon, Y., & Chun, W. (2017). Apocynin protects mesangial cells from lipopolysaccharide-induced inflammation by exerting heme oxygenase 1-mediated monocyte chemoattractant protein-1 suppression. International Journal of Molecular Medicine, 40, 1294-1301. https://doi.org/10.3892/ijmm.2017.3090
MLA
Bhatt, N. P., Park, J., Lee, H. J., Kim, S., Kwon, Y., Chun, W."Apocynin protects mesangial cells from lipopolysaccharide-induced inflammation by exerting heme oxygenase 1-mediated monocyte chemoattractant protein-1 suppression". International Journal of Molecular Medicine 40.4 (2017): 1294-1301.
Chicago
Bhatt, N. P., Park, J., Lee, H. J., Kim, S., Kwon, Y., Chun, W."Apocynin protects mesangial cells from lipopolysaccharide-induced inflammation by exerting heme oxygenase 1-mediated monocyte chemoattractant protein-1 suppression". International Journal of Molecular Medicine 40, no. 4 (2017): 1294-1301. https://doi.org/10.3892/ijmm.2017.3090