Interleukin 17A evoked mucosal damage is attenuated by cannabidiol and anandamide in a human colonic explant model.
Interleukin 17A (IL-17A) is a cytokine linked to inflammatory bowel disease. We investigated IL-17A expression in human colonic mucosa, whether IL-17A can elicit colonic mucosal damage in a human explant model and modulate gastrointestinal epithelial permeability in cell culture. We also tested if select cannabinoid ligands, shown to be protective in colitis models could attenuate damage caused by IL-17A. In addition, the ability of pro-inflammatory cytokines TNF-α and IL-1β to modulate levels of IL-17A in the explant colitis model was also explored. IL-17A incubation caused significant mucosal epithelial and crypt damage which were attenuated following hydrocortisone treatment, and also reduced following anandamide or cannabidiol incubation. IL-17A-evoked mucosal damage was also associated with an increase in matrix metalloprotease activity. However, IL-17A did not induce any significant changes in epithelial permeability in confluent Caco-2 cell monolayers over a 48h incubation period. IL-17A was located predominantly in human mucosal epithelium together with IL-17C, but both IL-17A and IL-17C were also expressed in the lamina propria and submucosa. Incubation of human colonic mucosal tissue or Caco-2 cells with pro-inflammatory cytokines TNF-α and IL-1β however did not alter IL-17A expression. These results indicate IL-17A has a widespread distribution in the human colon and the capacity to elicit mucosal damage which can be attenuated by cannabinoid ligands.
Discipline of Pharmacology, School of Medical Sciences, Faculty of Health Sciences, The University of Adelaide, South Australia, Australia.
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BS
Harvey
Department of Surgery, Flinders Medical Centre, Bedford Park, South Australia, Australia.
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Sia
Department of Surgery, Flinders Medical Centre, Bedford Park, South Australia, Australia.
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Wattchow
Discipline of Pharmacology, School of Medical Sciences, Faculty of Health Sciences, The University of Adelaide, South Australia, Australia. Electronic address: scott.smid@adelaide.edu.au.
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Smid
D001095:Arachidonic Acids / Q000494:pharmacology*; D015153:Blotting, Western; D018938:Caco-2 Cells; D002185:Cannabidiol / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D017097:Electric Impedance; D063388:Endocannabinoids / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D006801:Humans; D066298:In Vitro Techniques; D020381:Interleukin-17 / Q000009:adverse effects*; D053583:Interleukin-1beta / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology*; D008024:Ligands; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008954:Models, Biological; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D001095:Arachidonic Acids; D063388:Endocannabinoids; D020381:Interleukin-17; D053583:Interleukin-1beta; D008024:Ligands; D053284:Polyunsaturated Alkamides; D014409:Tumor Necrosis Factor-alpha; D002185:Cannabidiol; D020782:Matrix Metalloproteinases; C078814:anandamide
Anandamide; Cannabidiol; Colitis; Epithelial permeability; Interleukin 17