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Volume 25
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10.3390/molecules25030656
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Article

Marine Microorganism-Derived Macrolactins Inhibit Inflammatory Mediator Effects in LPS-Induced Macrophage and Microglial Cells by Regulating BACH1 and HO-1/Nrf2 Signals through Inhibition of TLR4 Activation

by
Eun-Nam Kim
1,†,
Ming Gao
2,†,
Hyukjae Choi
2,* and
Gil-Saeng Jeong
1,*
1
College of Pharmacy, Keimyung University, 1095 Dalgubeol-daero, Daegu 42601, Korea
2
College of Pharmacy, Yeungnam University, 280 Daehak-ro, Gyeongsan 38541, Korea
*
Authors to whom correspondence should be addressed.
†
These two authors contributed equally to this work.
Molecules 2020, 25(3), 656; https://doi.org/10.3390/molecules25030656
Submission received: 24 December 2019 / Revised: 31 January 2020 / Accepted: 1 February 2020 / Published: 4 February 2020
(This article belongs to the Section Bioorganic Chemistry)
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Abstract

Recently, many natural products with unique structure and promising pharmacological potential have been reported from marine-derived microorganisms. The macrolactin A (MA), 15-epi-dihydromacrolactin F (DMF) and macrolactin F (MF) were obtained from the culture broth extract of a marine sediment derived microorganism Bacillus sp. HC001. In this study, MA, DMF and MF inhibited the production and expression of proinflammatory mediators of inducible nitric oxide synthase (iNOS) and cyclooxygenase–2 (COX-2) in LPS-stimulated RAW264.7 and BV2 cells. Also, MA, DMF and MF exert anti-inflammatory effects through the expression of heme oxygenase (HO) -1, a stress-inducing enzyme that converts heme to carbon monoxide (CO), iron and biliberdine. Toll-like receptor 4 (TLR4) expressed by lipopolysaccharide (LPS) was inhibited by increased expression of HO-1 transcription factor Nrf2 and down regulation of BTB Domain And CNC Homolog 1 (BACH1), inhibited phosphorylation of Mitogen-activated protein kinase kinase kinase 7 (MAP3K7, TAK1) and nuclear factor kappaB (NF-κB). These results show that MA, DMF and MF effectively inhibited TLR4 by regulating BACH1 and HO-1/Nrf2 signals in LPS-stimulated RAW264.7 and BV2 cells, which suggests the possibility of use as an anti-inflammatory agent.
Keywords: heme oxygenase (HO)-1; nuclear factor erythroid 2-related factor 2 (Nrf2); BTB Domain and CNC Homolog 1 (BACH1); Toll-like receptor 4 (TLR4) heme oxygenase (HO)-1; nuclear factor erythroid 2-related factor 2 (Nrf2); BTB Domain and CNC Homolog 1 (BACH1); Toll-like receptor 4 (TLR4)

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MDPI and ACS Style

Kim, E.-N.; Gao, M.; Choi, H.; Jeong, G.-S. Marine Microorganism-Derived Macrolactins Inhibit Inflammatory Mediator Effects in LPS-Induced Macrophage and Microglial Cells by Regulating BACH1 and HO-1/Nrf2 Signals through Inhibition of TLR4 Activation. Molecules 2020, 25, 656. https://doi.org/10.3390/molecules25030656

AMA Style

Kim E-N, Gao M, Choi H, Jeong G-S. Marine Microorganism-Derived Macrolactins Inhibit Inflammatory Mediator Effects in LPS-Induced Macrophage and Microglial Cells by Regulating BACH1 and HO-1/Nrf2 Signals through Inhibition of TLR4 Activation. Molecules. 2020; 25(3):656. https://doi.org/10.3390/molecules25030656

Chicago/Turabian Style

Kim, Eun-Nam, Ming Gao, Hyukjae Choi, and Gil-Saeng Jeong. 2020. "Marine Microorganism-Derived Macrolactins Inhibit Inflammatory Mediator Effects in LPS-Induced Macrophage and Microglial Cells by Regulating BACH1 and HO-1/Nrf2 Signals through Inhibition of TLR4 Activation" Molecules 25, no. 3: 656. https://doi.org/10.3390/molecules25030656

APA Style

Kim, E.-N., Gao, M., Choi, H., & Jeong, G.-S. (2020). Marine Microorganism-Derived Macrolactins Inhibit Inflammatory Mediator Effects in LPS-Induced Macrophage and Microglial Cells by Regulating BACH1 and HO-1/Nrf2 Signals through Inhibition of TLR4 Activation. Molecules, 25(3), 656. https://doi.org/10.3390/molecules25030656

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