Anti-Inflammatory and Anti-Oxidative Activity of Indole-3-Acetic Acid Involves Induction of HO-1 and Neutralization of Free Radicals in RAW264.7 Cells

Ji, Yun; Yin, Wenzhen; Liang, Yuan; Sun, Lijun; Yin, Yue; Zhang, Weizhen

doi:10.3390/ijms21051579

Cited by 63 publications

(34 citation statements)

References 37 publications

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“…[90][91][92][93] Similarly, IAA has been linked to the reduction of inflammation in hepatocytes and macrophages, as well as the prevention of nonalcoholic fatty liver disease. 94,95 These observations suggest that diseases other than IBD may in fact be dependent on gut microbiota-derived metabolites, a concept supported by correlative studies that identify co-morbidity between IBD and extra-intestinal inflammatory disorders such as asthma and rheumatoid arthritis. 96,97 Future studies might consider the hypothesis that the manipulation of the gut microbiota and/or its metabolites may be a unified means of addressing varied inflammatory disorders.…”

Section: Discussionmentioning

confidence: 92%

“…IPA specifically has been previously assessed for its roles in ameliorating neurodegenerative disorders (such as Alzheimer's Disease) and chronic kidney disease 90‐93 . Similarly, IAA has been linked to the reduction of inflammation in hepatocytes and macrophages, as well as the prevention of nonalcoholic fatty liver disease 94,95 . These observations suggest that diseases other than IBD may in fact be dependent on gut microbiota‐derived metabolites, a concept supported by correlative studies that identify co‐morbidity between IBD and extra‐intestinal inflammatory disorders such as asthma and rheumatoid arthritis 96,97 .…”

Section: Discussionmentioning

confidence: 99%

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Microbial‐derived indoles inhibit neutrophil myeloperoxidase to diminish bystander tissue damage

et al. 2021

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During episodes of acute inflammation, polymorphonuclear leukocytes (PMNs) are actively recruited to sites of inflammation or injury where they provide anti-microbial and wound-healing functions. One enzyme crucial for fulfilling these functions is myeloperoxidase (MPO), which generates hypochlorous acid from Cl − and hydrogen peroxide. The potential exists, however, that uncontrolled the extracellular generation of hypochlorous acid by MPO can cause bystander tissue damage and inhibit the healing response. Previous work suggests that the microbiota-derived tryptophan metabolites 1H-indole and related molecules ("indoles") are protective during intestinal inflammation, although their precise mechanism of action is unclear. In the present work, we serendipitously discovered that indoles are potent and selective inhibitors of MPO. Using both primary human PMNs and recombinant human MPO in a cell-free system, we revealed that indoles inhibit MPO at physiologic concentrations. Particularly, indoles block the chlorinating activity of MPO, a reliable marker for MPO-associated tissue damage, as measured by coulometric-coupled HPLC. Further, we observed direct interaction between indoles and MPO using the established biochemical techniques microscale thermophoresis and STD-NMR. Utilizing a murine colitis model, we demonstrate that indoles inhibit bystander tissue damage, reflected in decreased colon 3-chlorotyrosine and pro-inflammatory chemokine expression in vivo. Taken together, these results identify microbiota-derived indoles that acts as endogenous immunomodulatory compounds through their actions on MPO, suggesting a symbiotic association between the gut microbiota and host innate immune system. Such findings offer exciting new targets for future pharmacological intervention.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Microbial‐derived indoles inhibit neutrophil myeloperoxidase to diminish bystander tissue damage

et al. 2021

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“…Study on rats revealed that IPA facilitated the protection against steatohepatitis induced by high-fat diet, as demonstrated by the improvement of gut dysbiosis and intestinal epithelial barrier function and the inhibition of pro-inflammatory signaling [118]. In addition, it has been shown that IAA displays anti-oxidative and anti-inflammatory activity, which is beneficial in the resistance to NAFLD induced by high-fat feeding and pro-inflammatory response in macrophages [119,120]. Interestingly, Bifidobacterium strains collected from human infants have been turned out to produce ILA [121], the favorable effect of these strains may be associated with ILA, which deserves to be corroborated in future studies.…”

Section: Functional Amino Acids (L-tryptophan and L-glutamine)mentioning

confidence: 99%

The Molecular and Mechanistic Insights Based on Gut–Liver Axis: Nutritional Target for Non-Alcoholic Fatty Liver Disease (NAFLD) Improvement

Yin

Sun

et al. 2020

IJMS

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Non-alcoholic fatty liver disease (NAFLD) is recognized as the most frequent classification of liver disease around the globe. Along with the sequencing technologies, gut microbiota has been regarded as a vital factor for the maintenance of human and animal health and the mediation of multiple diseases. The modulation of gut microbiota as a mechanism affecting the pathogenesis of NAFLD is becoming a growing area of concern. Recent advances in the communication between gut and hepatic tissue pave novel ways to better explain the molecular mechanisms regarding the pathological physiology of NAFLD. In this review, we recapitulate the current knowledge of the mechanisms correlated with the development and progression of NAFLD regulated by the gut microbiome and gut–liver axis, which may provide crucial therapeutic strategies for NAFLD. These mechanisms predominantly involve: (1) the alteration in gut microbiome profile; (2) the effects of components and metabolites from gut bacteria (e.g., lipopolysaccharides (LPS), trimethylamine-N-oxide (TMAO), and N,N,N-trimethyl-5-aminovaleric acid (TMAVA)); and (3) the impairment of intestinal barrier function and bile acid homeostasis. In particular, the prevention and therapy of NAFLD assisted by nutritional strategies are highlighted, including probiotics, functional oligosaccharides, dietary fibers, ω-3 polyunsaturated fatty acids, functional amino acids (L-tryptophan and L-glutamine), carotenoids, and polyphenols, based on the targets excavated from the gut–liver axis.

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“…Cytokine array analysis revealed that miR-154-5p was necessary for the expression of MCP1 increased by antigen stimulation (Figure 4A). ROS production contributes to an increased expression of MCP1 (34). OVA-induced allergic airway inflammation is also closely associated with the increased expression of MCP1 (35).…”

Section: Discussionmentioning

confidence: 99%

MiR-154-5p-MCP1 Axis Regulates Allergic Inflammation by Mediating Cellular Interactions

Kim

Kwon

et al. 2021

Front. Immunol.

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In a previous study, we have demonstrated that p62, a selective receptor of autophagy, can regulate allergic inflammation. In the present study, microRNA array analysis showed that miR-154-5p was increased by antigen (DNP-HSA) in a p62-dependent manner in rat basophilic leukemia cells (RBL2H3). NF-kB directly increased the expression of miR-154-5p. miR-154-5p mediated in vivo allergic reactions, including passive cutaneous anaphylaxis and passive systemic anaphylaxis. Cytokine array analysis showed that antigen stimulation increased the expression of MCP1 in RBL2H3 cells in an miR-154-5p-dependent manner. Reactive oxygen species (ROS)-ERK-NF-kB signaling increased the expression of MCP1 in antigen-stimulated RBL2H3 cells. Recombinant MCP1 protein induced molecular features of allergic reactions both in vitro and in vivo. Anaphylaxis-promoted tumorigenic potential has been known to be accompanied by cellular interactions involving mast cells, and macrophages, and cancer cells. Our experiments employing culture medium, co-cultures, and recombinant MCP1 protein showed that miR-154 and MCP1 mediated these cellular interactions. MiR-154-5p and MCP1 were found to be present in exosomes of RBL2H3 cells. Exosomes from PSA-activated BALB/C mouse induced molecular features of passive cutaneous anaphylaxis in an miR-154-5p-dependent manner. Exosomes from antigen-stimulated RBL2H3 cells enhanced both tumorigenic and metastatic potentials of B16F1 melanoma cells in an miR-154-5p-dependent manner. Exosomes regulated both ROS level and ROS mediated cellular interactions during allergic inflammation. Our results indicate that the miR-154-5p-MCP1 axis might serve as a valuable target for the development of anti-allergy therapeutics.

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Anti-Inflammatory and Anti-Oxidative Activity of Indole-3-Acetic Acid Involves Induction of HO-1 and Neutralization of Free Radicals in RAW264.7 Cells

Cited by 63 publications

References 37 publications

Microbial‐derived indoles inhibit neutrophil myeloperoxidase to diminish bystander tissue damage

Microbial‐derived indoles inhibit neutrophil myeloperoxidase to diminish bystander tissue damage

The Molecular and Mechanistic Insights Based on Gut–Liver Axis: Nutritional Target for Non-Alcoholic Fatty Liver Disease (NAFLD) Improvement

MiR-154-5p-MCP1 Axis Regulates Allergic Inflammation by Mediating Cellular Interactions

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