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10.4049/jimmunol.1401844

http://scihub22266oqcxt.onion/10.4049/jimmunol.1401844
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suck abstract from ncbi


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pmid25917103
      J+Immunol 2015 ; 194 (11 ): 5211-22
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  • Critical Role of Mast Cells and Peroxisome Proliferator-Activated Receptor ? in the Induction of Myeloid-Derived Suppressor Cells by Marijuana Cannabidiol In Vivo #MMPMID25917103
  • Hegde VL ; Singh UP ; Nagarkatti PS ; Nagarkatti M
  • J Immunol 2015[Jun]; 194 (11 ): 5211-22 PMID25917103 show ga
  • Cannabidiol (CBD) is a natural nonpsychotropic cannabinoid from marijuana (Cannabis sativa) with anti-epileptic and anti-inflammatory properties. Effect of CBD on naive immune system is not precisely understood. In this study, we observed that administering CBD into naive mice triggers robust induction of CD11b(+)Gr-1(+) myeloid-derived suppressor cells (MDSC) in the peritoneum, which expressed functional arginase 1, and potently suppressed T cell proliferation ex vivo. Furthermore, CBD-MDSC suppressed LPS-induced acute inflammatory response upon adoptive transfer in vivo. CBD-induced suppressor cells were comprised of CD11b(+)Ly6-G(+)Ly6-C(+) granulocytic and CD11b(+)Ly6-G(-)Ly6-C(+) monocytic subtypes, with monocytic MDSC exhibiting higher T cell-suppressive function. Induction of MDSC by CBD was markedly attenuated in Kit-mutant (Kit(W/W-v)) mast cell-deficient mice. MDSC response was reconstituted upon transfer of wild-type bone marrow-derived mast cells in Kit(W/W-v) mice, suggesting the key role of cKit (CD117) as well as mast cells. Moreover, mast cell activator compound 48/80 induced significant levels of MDSC in vivo. CBD administration in mice induced G-CSF, CXCL1, and M-CSF, but not GM-CSF. G-CSF was found to play a key role in MDSC mobilization inasmuch as neutralizing G-CSF caused a significant decrease in MDSC. Lastly, CBD enhanced the transcriptional activity of peroxisome proliferator-activated receptor ? in luciferase reporter assay, and PPAR-? selective antagonist completely inhibited MDSC induction in vivo, suggesting its critical role. Together, the results suggest that CBD may induce activation of PPAR-? in mast cells leading to secretion of G-CSF and consequent MDSC mobilization. CBD being a major component of Cannabis, our study indicates that marijuana may modulate or dysregulate the immune system by mobilizing MDSC.
  • |Animals [MESH]
  • |Anti-Inflammatory Agents/*pharmacology [MESH]
  • |Arginase/biosynthesis [MESH]
  • |CD11b Antigen/metabolism [MESH]
  • |Cannabidiol/*pharmacology [MESH]
  • |Cannabis/*metabolism [MESH]
  • |Cell Proliferation/drug effects [MESH]
  • |Chemokine CXCL1/biosynthesis [MESH]
  • |Female [MESH]
  • |Granulocyte Colony-Stimulating Factor/biosynthesis [MESH]
  • |Granulocyte-Macrophage Colony-Stimulating Factor/biosynthesis [MESH]
  • |Macrophage Colony-Stimulating Factor/biosynthesis [MESH]
  • |Mast Cells [MESH]
  • |Mice [MESH]
  • |Mice, Inbred C57BL [MESH]
  • |Mice, Knockout [MESH]
  • |Myeloid Cells/*immunology/metabolism [MESH]
  • |PPAR gamma/antagonists & inhibitors/*genetics [MESH]
  • |Receptors, Chemokine/metabolism [MESH]
  • |T-Lymphocytes/immunology [MESH]
  • |Transcriptional Activation/genetics [MESH]


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