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  1. Article ; Online: Aryl Hydrocarbon Receptor Regulates Muc2 Production Independently of IL-22 during Colitis.

    Saxena, Archana / Mitchell, Chandani / Bogdon, Raymond / Roark, Kasie / Wilson, Kiesha / Staley, Shanieka / Hailey, Michelle / Williams, Michal Claire / Rutkovsky, Alex / Nagarkatti, Prakash / Nagarkatti, Mitzi / Busbee, Philip Brandon

    International journal of molecular sciences

    2024  Volume 25, Issue 4

    Abstract: We previously reported that an aryl hydrocarbon receptor (AhR) ligand, indole-3-carbinol (I3C), was effective at reducing colitis severity through immune cell-mediated interleukin-22 (IL-22) production. Intestinal epithelial cells (IECs) are also ... ...

    Abstract We previously reported that an aryl hydrocarbon receptor (AhR) ligand, indole-3-carbinol (I3C), was effective at reducing colitis severity through immune cell-mediated interleukin-22 (IL-22) production. Intestinal epithelial cells (IECs) are also involved in regulating colitis, so we investigated their AhR-mediated mechanisms in the current report. A transcriptome analysis of IECs in wildtype (WT) mice revealed that during colitis, I3C regulated select mucin proteins, which could be attributed to goblet cell development. To address this, experiments under in vivo colitis (mice) or in vitro colon organoid conditions were undertaken to determine how select mucin proteins were altered in the absence or presence of AhR in IECs during I3C treatment. Comparing WT to IEC-specific AhR knockout mice (AhR
    MeSH term(s) Animals ; Mice ; Mucin-2/genetics ; Receptors, Aryl Hydrocarbon/metabolism ; Interleukin-22 ; Colitis/genetics ; Mucins/genetics ; Mice, Inbred C57BL
    Chemical Substances Mucin-2 ; Receptors, Aryl Hydrocarbon ; Interleukin-22 ; Mucins ; Muc2 protein, mouse
    Language English
    Publishing date 2024-02-18
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms25042404
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Alterations in the Gut Microbiome and Suppression of Histone Deacetylases by Resveratrol Are Associated with Attenuation of Colonic Inflammation and Protection Against Colorectal Cancer.

    Alrafas, Haider Rasheed / Busbee, Philip Brandon / Chitrala, Kumaraswamy Naidu / Nagarkatti, Mitzi / Nagarkatti, Prakash

    Journal of clinical medicine

    2020  Volume 9, Issue 6

    Abstract: Inflammatory bowel disease (IBD) is known to significantly increase the risk for development of colorectal cancer (CRC), suggesting inflammation and cancer development are closely intertwined. Thus, agents that suppress inflammation may prevent the onset ...

    Abstract Inflammatory bowel disease (IBD) is known to significantly increase the risk for development of colorectal cancer (CRC), suggesting inflammation and cancer development are closely intertwined. Thus, agents that suppress inflammation may prevent the onset of cancer. In the current study, we used resveratrol, an anti-inflammatory stilbenoid, to study the role of microbiota in preventing inflammation-driven CRC. Resveratrol treatment in the azoxymethane (AOM) and dextran sodium sulphate (DSS) CRC murine model caused an increase in anti-inflammatory CD4 + FOXP3 + (Tregs) and CD4 + IL10 + cells, a decrease in proinflammatory Th1 and Th17 cells, and attenuated CRC development. Gut microbial profile studies demonstrated that resveratrol altered the gut microbiome and short chain fatty acid (SCFA), with modest increases in n-butyric acid and a potential butyrate precursor isobutyric acid. Fecal transfer from resveratrol-treated CRC mice and butyrate supplementation resulted in attenuation of disease and suppression of the inflammatory T cell response. Data also revealed both resveratrol and sodium butyrate (BUT) were capable of inhibiting histone deacetylases (HDACs), correlating with Treg induction. Analysis of The Cancer Genome Atlas (TCGA) datasets revealed increased expression of Treg-specific transcription factor FoxP3 or anti-inflammatory IL-10 resulted in an increase in 5-year survival of patients with CRC. These data suggest that alterations in the gut microbiome lead to an anti-inflammatory T cell response, leading to attenuation of inflammation-driven CRC.
    Language English
    Publishing date 2020-06-09
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662592-1
    ISSN 2077-0383
    ISSN 2077-0383
    DOI 10.3390/jcm9061796
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: AhR Activation Leads to Alterations in the Gut Microbiome with Consequent Effect on Induction of Myeloid Derived Suppressor Cells in a CXCR2-Dependent Manner.

    Neamah, Wurood Hantoosh / Busbee, Philip Brandon / Alghetaa, Hasan / Abdulla, Osama A / Nagarkatti, Mitzi / Nagarkatti, Prakash

    International journal of molecular sciences

    2020  Volume 21, Issue 24

    Abstract: Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent ligand for AhR and a known carcinogen. While AhR activation by TCDD leads to significant immunosuppression, how this ... ...

    Abstract Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent ligand for AhR and a known carcinogen. While AhR activation by TCDD leads to significant immunosuppression, how this translates into carcinogenic signal is unclear. Recently, we demonstrated that activation of AhR by TCDD in naïve C57BL6 mice leads to massive induction of myeloid derived-suppressor cells (MDSCs). In the current study, we investigated the role of the gut microbiota in TCDD-mediated MDSC induction. TCDD caused significant alterations in the gut microbiome, such as increases in
    MeSH term(s) Animals ; Anti-Bacterial Agents/pharmacology ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Cells, Cultured ; DNA, Bacterial/genetics ; Dysbiosis/chemically induced ; Fecal Microbiota Transplantation/methods ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/drug effects ; Gastrointestinal Microbiome/genetics ; Mice ; Mice, Inbred C57BL ; Myeloid-Derived Suppressor Cells/metabolism ; Phylogeny ; Polychlorinated Dibenzodioxins/adverse effects ; Receptors, Aryl Hydrocarbon/metabolism ; Receptors, Interleukin-8B/metabolism ; Signal Transduction/drug effects ; T-Lymphocytes, Regulatory/immunology
    Chemical Substances Ahr protein, mouse ; Anti-Bacterial Agents ; Basic Helix-Loop-Helix Transcription Factors ; Cxcr2 protein, mouse ; DNA, Bacterial ; Polychlorinated Dibenzodioxins ; Receptors, Aryl Hydrocarbon ; Receptors, Interleukin-8B
    Language English
    Publishing date 2020-12-17
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms21249613
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The Ability of AhR Ligands to Attenuate Delayed Type Hypersensitivity Reaction Is Associated With Alterations in the Gut Microbiota.

    Abdulla, Osama A / Neamah, Wurood / Sultan, Muthanna / Alghetaa, Hasan K / Singh, Narendra / Busbee, Philip Brandon / Nagarkatti, Mitzi / Nagarkatti, Prakash

    Frontiers in immunology

    2021  Volume 12, Page(s) 684727

    Abstract: Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates T cell function. The aim of this study was to investigate the effects of AhR ligands, 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), and 6-Formylindolo[3,2-b]carbazole ...

    Abstract Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates T cell function. The aim of this study was to investigate the effects of AhR ligands, 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), and 6-Formylindolo[3,2-b]carbazole (FICZ), on gut-associated microbiota and T cell responses during delayed-type hypersensitivity (DTH) reaction induced by methylated bovine serum albumin (mBSA) in a mouse model. Mice with DTH showed significant changes in gut microbiota including an increased abundance of
    MeSH term(s) Animals ; Basic Helix-Loop-Helix Transcription Factors/agonists ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Butyric Acid/pharmacology ; Carbazoles/toxicity ; Cytokines/genetics ; Cytokines/metabolism ; Disease Models, Animal ; Female ; Gastrointestinal Microbiome/drug effects ; Hypersensitivity, Delayed/genetics ; Hypersensitivity, Delayed/immunology ; Hypersensitivity, Delayed/metabolism ; Hypersensitivity, Delayed/prevention & control ; Ligands ; Mice ; Mice, Inbred C57BL ; Polychlorinated Dibenzodioxins/toxicity ; Receptors, Aryl Hydrocarbon/agonists ; Receptors, Aryl Hydrocarbon/metabolism ; T-Lymphocytes, Regulatory/drug effects ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/metabolism ; Th17 Cells/drug effects ; Th17 Cells/immunology ; Th17 Cells/metabolism
    Chemical Substances 6-formylindolo(3,2-b)carbazole ; AHR protein, human ; Basic Helix-Loop-Helix Transcription Factors ; Carbazoles ; Cytokines ; Ligands ; Polychlorinated Dibenzodioxins ; Receptors, Aryl Hydrocarbon ; Butyric Acid (107-92-6)
    Language English
    Publishing date 2021-06-29
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2021.684727
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Combination of cannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), mitigates experimental autoimmune encephalomyelitis (EAE) by altering the gut microbiome.

    Al-Ghezi, Zinah Zamil / Busbee, Philip Brandon / Alghetaa, Hasan / Nagarkatti, Prakash S / Nagarkatti, Mitzi

    Brain, behavior, and immunity

    2019  Volume 82, Page(s) 25–35

    Abstract: Currently, a combination of marijuana cannabinoids including delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) is used as a drug to treat muscle spasticity in patients with Multiple Sclerosis (MS). Because these cannabinoids can also suppress ... ...

    Abstract Currently, a combination of marijuana cannabinoids including delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) is used as a drug to treat muscle spasticity in patients with Multiple Sclerosis (MS). Because these cannabinoids can also suppress inflammation, it is unclear whether such patients benefit from suppression of neuroinflammation and if so, what is the mechanism through which cannabinoids act. In the currently study, we used a murine model of MS, experimental autoimmune encephalomyelitis (EAE), to study the role of gut microbiota in the attenuation of clinical signs of paralysis and inflammation caused by cannabinoids. THC + CBD treatment attenuated EAE and caused significant decrease in inflammatory cytokines such as IL-17 and IFN-γ while promoting the induction of anti-inflammatory cytokines such as IL-10 and TGF-β. Use of 16S rRNA sequencing on bacterial DNA extracted from the gut revealed that EAE mice showed high abundance of mucin degrading bacterial species, such as Akkermansia muciniphila (A. muc), which was significantly reduced after THC + CBD treatment. Fecal Material Transfer (FMT) experiments confirmed that THC + CBD-mediated changes in the microbiome play a critical role in attenuating EAE. In silico computational metabolomics revealed that LPS biosynthesis, a key component in gram-negative bacteria such as A. muc, was found to be elevated in EAE mice which was confirmed by demonstrating higher levels of LPS in the brain, while treatment with THC + CBD reversed this trend. EAE mice treated with THC + CBD also had significantly higher levels of short chain fatty acids such as butyric, isovaleric, and valeric acids compared to naïve or disease controls. Collectively, our data suggest that cannabinoids may attenuate EAE and suppress neuroinflammation by preventing microbial dysbiosis seen during EAE and promoting healthy gut microbiota.
    MeSH term(s) Animals ; Cannabidiol/therapeutic use ; Cannabinoids/therapeutic use ; Cannabis/metabolism ; Cytokines/metabolism ; Disease Models, Animal ; Dronabinol/therapeutic use ; Dysbiosis/complications ; Encephalomyelitis, Autoimmune, Experimental/drug therapy ; Encephalomyelitis, Autoimmune, Experimental/immunology ; Encephalomyelitis, Autoimmune, Experimental/microbiology ; Female ; Gastrointestinal Microbiome/drug effects ; Gastrointestinal Microbiome/physiology ; Inflammation/complications ; Interferon-gamma/immunology ; Interleukin-17/metabolism ; Mice ; Mice, Inbred C57BL ; Multiple Sclerosis ; RNA, Ribosomal, 16S/genetics
    Chemical Substances Cannabinoids ; Cytokines ; Interleukin-17 ; RNA, Ribosomal, 16S ; Cannabidiol (19GBJ60SN5) ; Dronabinol (7J8897W37S) ; Interferon-gamma (82115-62-6)
    Language English
    Publishing date 2019-07-26
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 639219-2
    ISSN 1090-2139 ; 0889-1591
    ISSN (online) 1090-2139
    ISSN 0889-1591
    DOI 10.1016/j.bbi.2019.07.028
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 2276: Show issues Location:
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  6. Article: AhR Activation by TCDD (2,3,7,8-Tetrachlorodibenzo-p-dioxin) Attenuates Pertussis Toxin-Induced Inflammatory Responses by Differential Regulation of Tregs and Th17 Cells Through Specific Targeting by microRNA.

    Al-Ghezi, Zinah Zamil / Singh, Narendra / Mehrpouya-Bahrami, Pegah / Busbee, Philip Brandon / Nagarkatti, Mitzi / Nagarkatti, Prakash S

    Frontiers in microbiology

    2019  Volume 10, Page(s) 2349

    Abstract: The Aryl Hydrocarbon Receptor (AhR) is a transcription factor that, when activated by ligand-binding, has been shown to regulate the immune response. Pertussis Toxin (PTX) is a virulence factor found ... ...

    Abstract The Aryl Hydrocarbon Receptor (AhR) is a transcription factor that, when activated by ligand-binding, has been shown to regulate the immune response. Pertussis Toxin (PTX) is a virulence factor found in
    Language English
    Publishing date 2019-10-18
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2019.02349
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Endocannabinoid Anandamide Attenuates Acute Respiratory Distress Syndrome through Modulation of Microbiome in the Gut-Lung Axis.

    Sultan, Muthanna / Wilson, Kiesha / Abdulla, Osama A / Busbee, Philip Brandon / Hall, Alina / Carter, Taylor / Singh, Narendra / Chatterjee, Saurabh / Nagarkatti, Prakash / Nagarkatti, Mitzi

    Cells

    2021  Volume 10, Issue 12

    Abstract: Acute respiratory distress syndrome (ARDS) is a serious lung condition characterized by severe hypoxemia leading to limitations of oxygen needed for lung function. In this study, we investigated the effect of anandamide (AEA), an endogenous cannabinoid, ... ...

    Abstract Acute respiratory distress syndrome (ARDS) is a serious lung condition characterized by severe hypoxemia leading to limitations of oxygen needed for lung function. In this study, we investigated the effect of anandamide (AEA), an endogenous cannabinoid, on Staphylococcal enterotoxin B (SEB)-mediated ARDS in female mice. Single-cell RNA sequencing data showed that the lung epithelial cells from AEA-treated mice showed increased levels of antimicrobial peptides (AMPs) and tight junction proteins. MiSeq sequencing data on 16S RNA and LEfSe analysis demonstrated that SEB caused significant alterations in the microbiota, with increases in pathogenic bacteria in both the lungs and the gut, while treatment with AEA reversed this effect and induced beneficial bacteria. AEA treatment suppressed inflammation both in the lungs as well as gut-associated mesenteric lymph nodes (MLNs). AEA triggered several bacterial species that produced increased levels of short-chain fatty acids (SCFAs), including butyrate. Furthermore, administration of butyrate alone could attenuate SEB-mediated ARDS. Taken together, our data indicate that AEA treatment attenuates SEB-mediated ARDS by suppressing inflammation and preventing dysbiosis, both in the lungs and the gut, through the induction of AMPs, tight junction proteins, and SCFAs that stabilize the gut-lung microbial axis driving immune homeostasis.
    MeSH term(s) Animals ; Antimicrobial Peptides/metabolism ; Arachidonic Acids/pharmacology ; Arachidonic Acids/therapeutic use ; Butyrates/metabolism ; Cecum/pathology ; Cell Separation ; Colon/drug effects ; Colon/pathology ; Discriminant Analysis ; Dysbiosis/complications ; Dysbiosis/microbiology ; Endocannabinoids/pharmacology ; Endocannabinoids/therapeutic use ; Enterotoxins ; Female ; Gastrointestinal Microbiome ; Gastrointestinal Tract/drug effects ; Gastrointestinal Tract/pathology ; Lung/pathology ; Lymph Nodes/drug effects ; Lymph Nodes/pathology ; Lymphocyte Activation/drug effects ; Mice, Inbred C57BL ; Pneumonia/drug therapy ; Pneumonia/microbiology ; Polyunsaturated Alkamides/pharmacology ; Polyunsaturated Alkamides/therapeutic use ; Respiratory Distress Syndrome/complications ; Respiratory Distress Syndrome/drug therapy ; Respiratory Distress Syndrome/microbiology ; T-Lymphocytes/drug effects ; Mice
    Chemical Substances Antimicrobial Peptides ; Arachidonic Acids ; Butyrates ; Endocannabinoids ; Enterotoxins ; Polyunsaturated Alkamides ; enterotoxin B, staphylococcal (39424-53-8) ; anandamide (UR5G69TJKH)
    Language English
    Publishing date 2021-11-25
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells10123305
    Database MEDical Literature Analysis and Retrieval System OnLINE

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