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Article ; Online: Yin and yang of cannabinoid CB1 receptor: CB1 deletion in immune cells causes exacerbation while deletion in non-immune cells attenuates obesity.

Miranda, Kathryn / Becker, William / Busbee, Philip B / Dopkins, Nicholas / Abdulla, Osama A / Zhong, Yin / Zhang, Jiajia / Nagarkatti, Mitzi / Nagarkatti, Prakash S

iScience

2022 Volume 25, Issue 9, Page(s) 104994

Abstract: While blockade of cannabinoid receptor 1 (CB1) has been shown to attenuate diet-induced obesity (DIO), its relative role in different cell types has not been tested. The current study investigated the role of CB1 in immune vs non-immune cells during DIO ... ...

Abstract	While blockade of cannabinoid receptor 1 (CB1) has been shown to attenuate diet-induced obesity (DIO), its relative role in different cell types has not been tested. The current study investigated the role of CB1 in immune vs non-immune cells during DIO by generating radiation-induced bone marrow chimeric mice that expressed functional CB1 in all cells except the immune cells or expressed CB1 only in immune cells. CB1
Language	English
Publishing date	2022-08-24
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2022.104994
Database	MEDical Literature Analysis and Retrieval System OnLINE

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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
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Article: The Endocannabinoid Anandamide Attenuates Acute Respiratory Distress Syndrome by Downregulating miRNA that Target Inflammatory Pathways.

Sultan, Muthanna / Alghetaa, Hasan / Mohammed, Amirah / Abdulla, Osama A / Wisniewski, Paul J / Singh, Narendra / Nagarkatti, Prakash / Nagarkatti, Mitzi

Frontiers in pharmacology

2021 Volume 12, Page(s) 644281

Abstract: Acute respiratory distress syndrome (ARDS) is defined as a type of respiratory failure that is caused by a variety of insults such as pneumonia, sepsis, trauma and certain viral infections. In this study, we investigated the effect of an endocannabinoid, ...

Abstract	Acute respiratory distress syndrome (ARDS) is defined as a type of respiratory failure that is caused by a variety of insults such as pneumonia, sepsis, trauma and certain viral infections. In this study, we investigated the effect of an endocannabinoid, anandamide (AEA), on ARDS induced in the mouse by
Language	English
Publishing date	2021-04-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2021.644281
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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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Article ; Online: AhR Ligands Differentially Regulate miRNA-132 Which Targets HMGB1 and to Control the Differentiation of Tregs and Th-17 Cells During Delayed-Type Hypersensitivity Response.

Abdulla, Osama A / Neamah, Wurood / Sultan, Muthanna / Chatterjee, Saurabh / Singh, Narendra / Nagarkatti, Mitzi / Nagarkatti, Prakash

Frontiers in immunology

2021 Volume 12, Page(s) 635903

Abstract: Aryl hydrocarbon receptor (AhR), is a transcription factor and an environmental sensor that has been shown to regulate T cell differentiation. Interestingly, AhR ligands exert varying effects from suppression to exacerbation of inflammation through ... ...

Abstract	Aryl hydrocarbon receptor (AhR), is a transcription factor and an environmental sensor that has been shown to regulate T cell differentiation. Interestingly, AhR ligands exert varying effects from suppression to exacerbation of inflammation through induction of Tregs and Th-17 cells, respectively. In the current study, we investigated whether the differential effects of AhR ligands on T cell differentiation are mediated by miRNA during delayed-type hypersensitivity (DTH) reaction against methylated Bovine Serum Albumin (mBSA). Treatment of C57BL/6 mice with TCDD attenuated mBSA-mediated DTH response, induced Tregs, decreased Th-17 cells, and caused upregulation of miRNA-132. TCDD caused an increase in several Treg subsets including inducible peripheral, natural thymic, and Th3 cells. Also, TCDD increased TGF-β and Foxp3 expression. In contrast, treating mice with FICZ exacerbated the DTH response, induced inflammatory Th17 cells, induced IL-17, and RORγ. Analysis of miRNA profiles from draining lymph nodes showed that miR-132 was upregulated in the TCDD group and downregulated in the FICZ group. Transfection studies revealed that miRNA-132 targeted High Mobility Group Box 1 (HMGB1). Downregulation of HMGB1 caused an increase in FoxP3+ Treg differentiation and suppression of Th-17 cells while upregulation of HMGB1 caused opposite effects. Moreover, TCDD was less effective in suppressing DTH response and induction of Tregs in mice that were deficient in miR-132. In summary, this study demonstrates that TCDD and FICZ have divergent effects on DTH response and T cell differentiation, which is mediated through, at least in part, regulation of miRNA-132 that targets HMGB1.
MeSH term(s)	Animals ; Basic Helix-Loop-Helix Transcription Factors/agonists ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Carbazoles/toxicity ; Cell Differentiation/drug effects ; Cells, Cultured ; Cytokines/genetics ; Cytokines/metabolism ; Disease Models, Animal ; Female ; Forkhead Transcription Factors/genetics ; Forkhead Transcription Factors/metabolism ; HMGB1 Protein/genetics ; HMGB1 Protein/metabolism ; Hypersensitivity, Delayed/genetics ; Hypersensitivity, Delayed/immunology ; Hypersensitivity, Delayed/metabolism ; Hypersensitivity, Delayed/prevention & control ; Ligands ; Mice, Inbred C57BL ; Mice, Knockout ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Phenotype ; 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 ; Mice
Chemical Substances	6-formylindolo(3,2-b)carbazole ; Ahr protein, mouse ; Basic Helix-Loop-Helix Transcription Factors ; Carbazoles ; Cytokines ; Forkhead Transcription Factors ; Foxp3 protein, mouse ; HMGB1 Protein ; HMGB1 protein, mouse ; Ligands ; MIRN132 microRNA, mouse ; MicroRNAs ; Polychlorinated Dibenzodioxins ; Receptors, Aryl Hydrocarbon
Language	English
Publishing date	2021-02-19
Publishing country	Switzerland
Document type	Comparative Study ; Journal Article ; 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.2021.635903
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Dysregulated TP53 Among PTSD Patients Leads to Downregulation of miRNA let-7a and Promotes an Inflammatory Th17 Phenotype.

Busbee, Philip B / Bam, Marpe / Yang, Xiaoming / Abdulla, Osama A / Zhou, Juhua / Ginsberg, Jay Paul Jack / Aiello, Allison E / Uddin, Monica / Nagarkatti, Mitzi / Nagarkatti, Prakash S

Frontiers in immunology

2022 Volume 12, Page(s) 815840

Abstract: Post-traumatic stress disorder (PTSD) is a psychiatric disorder and patients diagnosed with PTSD often express other comorbid health issues, particularly autoimmune and inflammatory disorders. Our previous reports investigating peripheral blood ... ...

Abstract	Post-traumatic stress disorder (PTSD) is a psychiatric disorder and patients diagnosed with PTSD often express other comorbid health issues, particularly autoimmune and inflammatory disorders. Our previous reports investigating peripheral blood mononuclear cells (PBMCs) from PTSD patients showed that these patients exhibit an increased inflammatory T helper (Th) cell phenotype and widespread downregulation of microRNAs (miRNAs), key molecules involved in post-transcriptional gene regulation. A combination of analyzing prior datasets on gene and miRNA expression of PBMCs from PTSD and Control samples, as well as experiments using primary PBMCs collected from human PTSD and Controls blood, was used to evaluate TP53 expression, DNA methylation, and miRNA modulation on Th17 development. In the current report, we note several downregulated miRNAs were linked to tumor protein 53 (TP53), also known as p53. Expression data from PBMCs revealed that compared to Controls, PTSD patients exhibited decreased TP53 which correlated with an increased inflammatory Th17 phenotype. Decreased expression of TP53 in the PTSD population was shown to be associated with an increase in DNA methylation in the
MeSH term(s)	Adult ; Biomarkers ; DNA Methylation ; Female ; Gene Expression Regulation ; Humans ; Immunophenotyping ; Leukocytes, Mononuclear/immunology ; Leukocytes, Mononuclear/metabolism ; Lymphocyte Activation ; Male ; MicroRNAs/genetics ; Middle Aged ; Phenotype ; Promoter Regions, Genetic ; RNA Interference ; Severity of Illness Index ; Stress Disorders, Post-Traumatic/diagnosis ; Stress Disorders, Post-Traumatic/etiology ; Stress Disorders, Post-Traumatic/metabolism ; Th17 Cells/immunology ; Th17 Cells/metabolism ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism
Chemical Substances	Biomarkers ; MicroRNAs ; Tumor Suppressor Protein p53 ; mirnlet7 microRNA, human
Language	English
Publishing date	2022-01-04
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.815840
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: AhR Activation Leads to Massive Mobilization of Myeloid-Derived Suppressor Cells with Immunosuppressive Activity through Regulation of CXCR2 and MicroRNA miR-150-5p and miR-543-3p That Target Anti-Inflammatory Genes.

Neamah, Wurood Hantoosh / Singh, Narendra P / Alghetaa, Hasan / Abdulla, Osama A / Chatterjee, Saurabh / Busbee, Philip B / Nagarkatti, Mitzi / Nagarkatti, Prakash

Journal of immunology (Baltimore, Md. : 1950)

2019 Volume 203, Issue 7, Page(s) 1830–1844

Abstract: The compound 2,3,7,8-tetrachlorodibenzo- ...

Abstract	The compound 2,3,7,8-tetrachlorodibenzo-
MeSH term(s)	Animals ; Basic Helix-Loop-Helix Transcription Factors/agonists ; Basic Helix-Loop-Helix Transcription Factors/immunology ; Chemokines/immunology ; Female ; Gene Expression Regulation/drug effects ; Gene Expression Regulation/immunology ; Immune Tolerance ; Inflammation/chemically induced ; Inflammation/immunology ; Inflammation/pathology ; Mice ; MicroRNAs ; Myeloid-Derived Suppressor Cells/immunology ; Myeloid-Derived Suppressor Cells/pathology ; Polychlorinated Dibenzodioxins/toxicity ; Receptors, Aryl Hydrocarbon/agonists ; Receptors, Aryl Hydrocarbon/immunology ; Receptors, Interleukin-8B/immunology
Chemical Substances	Ahr protein, mouse ; Basic Helix-Loop-Helix Transcription Factors ; Chemokines ; MicroRNAs ; Mirn150 microRNA, mouse ; Polychlorinated Dibenzodioxins ; Receptors, Aryl Hydrocarbon ; Receptors, Interleukin-8B
Language	English
Publishing date	2019-09-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.1900291
Database	MEDical Literature Analysis and Retrieval System OnLINE

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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
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Article ; Online: Yin and yang of cannabinoid CB1 receptor: CB1 deletion in immune cells causes exacerbation while deletion in non-immune cells attenuates obesity.

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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.

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Article: The Endocannabinoid Anandamide Attenuates Acute Respiratory Distress Syndrome by Downregulating miRNA that Target Inflammatory Pathways.

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

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Article ; Online: AhR Ligands Differentially Regulate miRNA-132 Which Targets HMGB1 and to Control the Differentiation of Tregs and Th-17 Cells During Delayed-Type Hypersensitivity Response.

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Article ; Online: Dysregulated TP53 Among PTSD Patients Leads to Downregulation of miRNA let-7a and Promotes an Inflammatory Th17 Phenotype.

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Article ; Online: AhR Activation Leads to Massive Mobilization of Myeloid-Derived Suppressor Cells with Immunosuppressive Activity through Regulation of CXCR2 and MicroRNA miR-150-5p and miR-543-3p That Target Anti-Inflammatory Genes.

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

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