Production of endocannabinoids by activated T cells and B cells modulates inflammation associated with delayed‐type hypersensitivity

Sido, Jessica M.; Nagarkatti, Prakash; Nagarkatti, Mitzi

doi:10.1002/eji.201546181

Cited by 35 publications

(29 citation statements)

References 33 publications

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“…Tissue lipids were extracted as described earlier 15 . Extracted lipid from serum and adipose tissue was processed as previously described 53 . The levels of endocannabinoids from tissue and serum were quantified by triple quadrupole mass spectrometer with electrospray ionization at the Mass Spectrometry Center at the Department of Chemistry and Biochemistry, University of South Carolina.…”

Section: Methodsmentioning

confidence: 99%

Blockade of CB1 cannabinoid receptor alters gut microbiota and attenuates inflammation and diet-induced obesity

Mehrpouya-Bahrami¹,

Chitrala²,

Ganewatta

et al. 2017

Sci Rep

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131

107

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Obesity is characterized by chronic low-grade, systemic inflammation, altered gut microbiota, and gut barrier disruption. Additionally, obesity is associated with increased activity of endocannabinoid system (eCB). However, the clear connection between gut microbiota and the eCB system in the regulation of energy homeostasis and adipose tissue inflammation and metabolism, remains to be established. We investigated the effect of treatment of mice with a cannabinoid receptor 1 (CB1) antagonist on Diet-Induced Obesity (DIO), specifically whether such a treatment that blocks endocannabinoid activity can induce changes in gut microbiota and anti-inflammatory state in adipose tissue. Blockade of CB1 attenuated DIO, inflammatory cytokines and trafficking of M1 macrophages into adipose tissue. Decreased inflammatory tone was associated with a lower intestinal permeability and decreased metabolic endotoxemia as evidenced by reduced plasma LPS level, and improved hyperglycemia and insulin resistance. 16S rRNA metagenomics sequencing revealed that CB1 blockade dramatically increased relative abundance of Akkermansia muciniphila and decreased Lanchnospiraceae and Erysipelotrichaceae in the gut. Together, the current study suggests that blocking of CB1 ameliorates Diet-Induced Obesity and metabolic disorder by modulating macrophage inflammatory mediators, and that this effect is associated with alterations in gut microbiota and their metabolites.

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Section: Methodsmentioning

confidence: 99%

Blockade of CB1 cannabinoid receptor alters gut microbiota and attenuates inflammation and diet-induced obesity

Mehrpouya-Bahrami¹,

Chitrala²,

Ganewatta

et al. 2017

Sci Rep

Self Cite

131

107

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“…Similarly, rats with acute pancreatitis also exhibit significantly elevated circulating AEA concentrations, particularly in animals with a severe, necrotizing pancreatitis (Matsuda et al, 2005). When activated, macrophages (Di Marzo et al, 1999;Varga et al, 1998), platelets (Varga et al, 1998), T and B cells (Sido et al, 2016) release endocannabinoids ex vivo, and so could be a source of circulating endocannabinoids. On the other hand, a recent study carried out in patients undergoing hematopoietic stem cell transplantation (HCT) suggests that bone marrow-derived immune cells per se may not be an important source of 2-AG (Knight et al, 2015).…”

Section: Circulating Endocannabinoids and Inflammationmentioning

confidence: 99%

Circulating Endocannabinoids: From Whence Do They Come and Where are They Going?

Hillard

2017

Neuropsychopharmacol.

347

241

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The goal of this review is to summarize studies in which concentrations of circulating endocannabinoids in humans have been examined in relationship to physiological measurements and pathological status. The roles of endocannabinoids in the regulation of energy intake and storage have been well studied and the data obtained consistently support the hypothesis that endocannabinoid signaling is associated with increased consumption and storage of energy. Physical exercise mobilizes endocannabinoids, which could contribute to refilling of energy stores and also to the analgesic and mood-elevating effects of exercise. Circulating concentrations of 2-arachidonoylglycerol are very significantly circadian and dysregulated when sleep is disrupted. Other conditions under which circulating endocannabinoids are altered include inflammation and pain. A second important role for endocannabinoid signaling is to restore homeostasis following stress. Circulating endocannabinoids are stress-responsive and there is evidence that their concentrations are altered in disorders associated with excessive stress, including post-traumatic stress disorder. Although determination of circulating endocannabinoids can provide important information about the state of endocannabinoid signaling and thus allow for hypotheses to be defined and tested, the large number of physiological factors that contribute to their circulating concentrations makes it difficult to use them in isolation as a biomarker for a specific disorder.

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“…swelling, and regulated the cytotoxicity of NK cells and the proliferation of lymphocytes. The cytotoxicity of NK cells, the DTH test and T lymphocyte proliferation are considered important assessment criteria of immunity in an animal (25). When an antigen is exposed in humoral immune response, opsonophagocytosis is mediated by IgA and IgG which are evidently enhanced among total Igs (26).…”

Section: Discussionmentioning

confidence: 99%

Investigation of the immunomodulatory activity of Tricholoma matsutake mycelium in cyclophosphamide-induced immunosuppressed mice

Wang

Teng

et al. 2017

Molecular Medicine Reports

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Tricholoma matsutake, a popular food and biopharmaceutical resource in Asia, possesses various pharmacological activities. Although T. matsutake mycelium (TM) may enhance immunity, previous studies, to the best of our knowledge, have been performed on normal animals or cells alone. The present study aimed to evaluate the immunomodulatory activity of TM at doses of 0.3, 1.0 and 2.0 g/kg in cyclophosphamide (CTX)‑induced immunosuppressed mouse models. TM treatment for 2 weeks markedly improved the gain in bodyweight, increased organ indices, reduced hind paw swelling and positively regulated the cytotoxicity of natural killer cells and the proliferation of lymphocytes. These effects are similar to that of thymosin α1 (0.16 mg/kg) which served as the positive control. In CTX‑induced immunosuppressed mice, TM demonstrated marked effects on the modulation of the production of immunoglobulin (Ig)G and IgA, and the levels of interleukin‑2, 6, 10 and 12, interferon‑α and γ and tumor necrosis factor‑α in serum. Compared with CTX mice, the reduced activity of nuclear factor (NF)‑κB in serum and spleen, and phosphorylation of inhibitor of NF‑κB kinase α/β in spleen were observed in TM‑treated mice. Taken together, TM effectively improved immune function in immunosuppressed mice via modulation of ILs and inflammatory factors associated with the NF‑κB signaling pathway.

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Production of endocannabinoids by activated T cells and B cells modulates inflammation associated with delayed‐type hypersensitivity

Cited by 35 publications

References 33 publications

Blockade of CB1 cannabinoid receptor alters gut microbiota and attenuates inflammation and diet-induced obesity

Blockade of CB1 cannabinoid receptor alters gut microbiota and attenuates inflammation and diet-induced obesity

Circulating Endocannabinoids: From Whence Do They Come and Where are They Going?

Investigation of the immunomodulatory activity of Tricholoma matsutake mycelium in cyclophosphamide-induced immunosuppressed mice

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