Anandamide attenuates Th-17 cell-mediated delayed-type hypersensitivity response by triggering IL-10 production and consequent microRNA induction.
Endogenous cannabinoids [endocannabinoids] are lipid signaling molecules that have been shown to modulate immune functions. However, their role in the regulation of Th17 cells has not been studied previously. In the current study, we used methylated Bovine Serum Albumin [mBSA]-induced delayed type hypersensitivity [DTH] response in C57BL/6 mice, mediated by Th17 cells, as a model to test the anti-inflammatory effects of endocannabinoids. Administration of anandamide [AEA], a member of the endocannabinoid family, into mice resulted in significant mitigation of mBSA-induced inflammation, including foot pad swelling, cell infiltration, and cell proliferation in the draining lymph nodes [LN]. AEA treatment significantly reduced IL-17 and IFN-γ production, as well as decreased RORγt expression while causing significant induction of IL-10 in the draining LNs. IL-10 was critical for the AEA-induced mitigation of DTH response inasmuch as neutralization of IL-10 reversed the effects of AEA. We next analyzed miRNA from the LN cells and found that 100 out of 609 miRNA species were differentially regulated in AEA-treated mice when compared to controls. Several of these miRNAs targeted proinflammatory mediators. Interestingly, many of these miRNA were also upregulated upon in vitro treatment of LN cells with IL-10. Together, the current study demonstrates that AEA may suppress Th-17 cell-mediated DTH response by inducing IL-10 which in turn triggers miRNA that target proinflammatory pathways.
Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, United States of America.
Austin R
AR
Jackson
Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, United States of America.
Prakash
P
Nagarkatti
Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, United States of America.
Mitzi
M
Nagarkatti
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D063388:Endocannabinoids / Q000494:pharmacology* / Q000627:therapeutic use; D006968:Hypersensitivity, Delayed / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D053284:Polyunsaturated Alkamides / Q000494:pharmacology* / Q000627:therapeutic use; D058504:Th17 Cells / Q000187:drug effects* / Q000378:metabolism
D001095:Arachidonic Acids; D016207:Cytokines; D063388:Endocannabinoids; D035683:MicroRNAs; D053284:Polyunsaturated Alkamides; D016753:Interleukin-10; C078814:anandamide