BML-111 accelerates the resolution of inflammation by modulating the Nrf2/HO-1 and NF-κB pathways in rats with ventilator-induced lung injury

Xu, Jiqian; Li, Hongbin; Chen, Lin; Wang, Yaxin; Lu, Shengzhong; Li, Shengnan; Cui, Shu-Nan; Xiao, Huang; Qin, Lu; Hu, Houxiang; Yao, Shanglong; Shang, You

doi:10.1016/j.intimp.2019.02.005

Cited by 18 publications

(8 citation statements)

References 36 publications

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“…Pro-resolving lipid mediators such as RvD1 [18] and LXA4 [16] have the ability to counteract the deleterious effects of UVB by increasing Nrf2 signaling. Our data also corroborate findings in a model of ventilator-induced lung injury, in which BML-111 increased Nrf2/HO-1 expression and reduced NF-κB activation in the lungs of rats [21]. These data and our results further indicate that an increase on Nrf2 activation (and decrease on NF-κB-dependent pro-inflammatory mediators) is a BML-111 mechanism to reduce inflammation.…”

Section: Discussionsupporting

confidence: 90%

“…Given that SPMs can be chemically unstable and often inactivated within tissues near the site of formation [19], stable analogs are required. BML-111 (5(S)-6(R)-7-trihydroxyheptanoic acid methyl ester) is a commercially available synthetic ALX/FPR2 receptor agonist with analgesic, antioxidant, and anti-inflammatory properties [20][21][22]. Specifically for skin inflammation, treatment with BML-111 attenuates epidermal hyperplasia and pro-inflammatory cytokine production in a model of imiquimod (IMQ)-induced psoriasis [22].…”

Section: Introductionmentioning

confidence: 99%

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The Lipoxin Receptor/FPR2 Agonist BML-111 Protects Mouse Skin Against Ultraviolet B Radiation

et al. 2020

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Excessive exposure to UV, especially UVB, is the most important risk factor for skin cancer and premature skin aging. The identification of the specialized pro-resolving lipid mediators (SPMs) challenged the preexisting paradigm of how inflammation ends. Rather than a passive process, the resolution of inflammation relies on the active production of SPMs, such as Lipoxins (Lx), Maresins, protectins, and Resolvins. LXA4 is an SPM that exerts its action through ALX/FPR2 receptor. Stable ALX/FPR2 agonists are required because SPMs can be quickly metabolized within tissues near the site of formation. BML-111 is a commercially available synthetic ALX/FPR2 receptor agonist with analgesic, antioxidant, and anti-inflammatory properties. Based on that, we aimed to determine the effect of BML-111 in a model of UVB-induced skin inflammation in hairless mice. We demonstrated that BML-111 ameliorates the signs of UVB-induced skin inflammation by reducing neutrophil recruitment and mast cell activation. Reduction of these cells by BML-111 led to lower number of sunburn cells formation, decrease in epidermal thickness, collagen degradation, cytokine production (TNF-α, IL-1β, IL-6, TGF, and IL-10), and oxidative stress (observed by an increase in total antioxidant capacity and Nrf2 signaling pathway), indicating that BML-111 might be a promising drug to treat skin disorders.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

The Lipoxin Receptor/FPR2 Agonist BML-111 Protects Mouse Skin Against Ultraviolet B Radiation

et al. 2020

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“…nF-κB signaling is essential for the regulation of the inflammatory response in sepsis-induced ali (35), and activation of the nrf2/Ho-1 signaling pathway may relieve sepsis-induced ALI by suppressing inflammation and oxidative stress (36,37). increasing evidence has demonstrated that regulation of the nrf2/Ho-1 and nF-κB signaling pathways alleviates lung injury induced by ventilator, by suppressing inflammation and oxidative stress (38). in order to further investigate the molecular mechanisms underlying sufentanil in ali, the expression levels of nF-κB and nrf2/Ho-1 signaling pathway proteins were measured via western blot analysis, following overexpression of KnG1 in lPS-stimulated aec ii.…”

Section: Discussionmentioning

confidence: 99%

Sufentanil attenuates inflammation and oxidative stress in sepsis-induced acute lung injury by downregulating KNG1 expression

Wang

Han

et al. 2020

Mol Med Rep

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The present study aimed to investigate the effects of sufentanil on sepsis-induced acute lung injury (ali), and identify the potential molecular mechanisms underlying its effect. in order to achieve this, a rat sepsis model was established. Following treatment with sufentanil, the lung wet/dry (W/d) weight ratio was calculated. Histopathological analysis was performed via hematoxylin and eosin staining. Levels of inflammatory factors in bronchoalveolar lavage fluid were determined via eliSa. Furthermore, malondialdehyde (Mda) content and the activities of superoxide dismutase (Sod), catalase (caT) and glutathione peroxidase (GSH-Px) in tissue homogenates were assessed using commercial kits. Western blot analysis was performed to determine kininogen-1 (KnG1) protein expression. in addition, alveolar epithelial type ii cells (aec ii) were stimulated with lipopolysaccharide (LPS) to mimic ALI. The levels of inflammation and oxidative stress were evaluated following overexpression of KnG1. Protein expression levels of nuclear factor-κB (nF-κB) and nuclear factor erythroid 2-related factor 2 (nrf2)/heme oxygenase-1 (Ho-1) signaling were determined via western blot analysis. The results of the present study demonstrated that sufentanil alleviated histopathological injury and the W/d ratio in lung tissue. Following treatment with sufentanil, levels of inflammatory factors also decreased, accompanied by decreased concentrations of Mda, and increased activities of Sod, caT and GSH-Px. notably, KnG1 was decreased in lung tissues following treatment with sufentanil. Furthermore, overexpression of KnG1 attenuated the inhibitory effects of sufentanil on lPS-induced inflammation and oxidative stress in aec ii. Sufentanil markedly downregulated nF-κB expression, while upregulating nrf2 and Ho-1 expression levels, which was reversed following overexpression of KnG1. Taken together, the results of the present study suggested that sufentanil may alleviate inflammation and oxidative stress in sepsis-induced ali by downregulating KnG1 expression.

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“…The LXA4 receptor agonists suppressed the inflammatory activities to protect inflammatory diseases [20,21]. BML-111, which is a LXA4 receptor agonist, has reported to protect against acute lung injury by reducing inflammation and oxidative stress [22,23]. However, it is unknown whether BML-111 can alleviate inflammation and oxidative damage in SCI.…”

Section: Introductionmentioning

confidence: 99%

The Lipoxin A4 Receptor Agonist BML-111 Alleviates Inflammatory Injury and Oxidative Stress in Spinal Cord Injury

Liu

Peng

2020

Med Sci Monit

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Departmental sources Background: Spinal cord injury (SCI) has a high incidence and causes serious harm. Lipoxin A4 (LXA4) receptor agonist BML-111 was reported to regulate inflammation and oxidative stress. The goal of this study was to assess whether BML-111 could protect against SCI by suppressing inflammation and oxidative stress. Material/Methods: We developed a rat SCI model, then BML-111 was intraperitoneally injected into SCI rats to observe the BML-111 function. The pathological changes of SCI were observed with hematoxylin and eosin (HE) staining. Motor function of rats were assessed by the modified Tarlov's scale. ELISA was used to assess the changes in levels of TNF-a, IL-1b, and IL-6. Western blot analysis was performed to assess the expressions of TNF-a, IL-1b, IL-6, Bcl2, Bax, and cleaved caspase3 in spinal cord tissue. TOS and TAS in rat serum were detected by xylenol orange method and ABTS method, respectively. The apoptotic cells in spinal cord tissue were observed with TUNEL assay. Results: The results indicated that BML-111 effectively improved the SCI and motor function of rats. BML-111 treatment decreased the levels of TNF-a, IL-1b, and IL-6 in serum and spinal cord tissue, as well as decreasing the levels of TOS and TAS and cell apoptosis. Conclusions: BML-111 alleviated inflammation and oxidative stress in SCI rats.

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BML-111 accelerates the resolution of inflammation by modulating the Nrf2/HO-1 and NF-κB pathways in rats with ventilator-induced lung injury

Cited by 18 publications

References 36 publications

The Lipoxin Receptor/FPR2 Agonist BML-111 Protects Mouse Skin Against Ultraviolet B Radiation

The Lipoxin Receptor/FPR2 Agonist BML-111 Protects Mouse Skin Against Ultraviolet B Radiation

Sufentanil attenuates inflammation and oxidative stress in sepsis-induced acute lung injury by downregulating KNG1 expression

The Lipoxin A4 Receptor Agonist BML-111 Alleviates Inflammatory Injury and Oxidative Stress in Spinal Cord Injury

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