Interleukin 17A evoked mucosal damage is attenuated by cannabidiol and anandamide in a human colonic explant model

Harvey, Benjamin S.; Sia, Tiong Cheng; Wattchow, David; Smid, Scott D.

doi:10.1016/j.cyto.2013.10.006

Cited by 30 publications

(25 citation statements)

References 53 publications

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“…Several immunohistochemical studies using clinical samples have indicated that IL-17C is expressed mainly in the epithelial cells, including for inflammatory bowel disease (IBD) (33,34), chronic obstructive pulmonary disease (20), chronic rhinosinusitis with nasal polyposis (35), and recurrent aphthous ulcer (36). Similar to other tissues, our results revealed that IL-17C was present predominantly in the epithelial cells of H. pylori-infected gastric biopsy specimens as well as in chromogranin A-positive endocrine cells (mainly G cells).…”

Section: Discussionmentioning

confidence: 99%

Interleukin-17C in Human Helicobacter pylori Gastritis

et al. 2017

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The interleukin-17 (IL-17) family of cytokines (IL-17A to IL-17F) is involved in many inflammatory diseases. Although IL-17A is recognized as being involved in the pathophysiology of Helicobacter pylori-associated diseases, the role of other IL-17 cytokine family members remains unclear. Microarray analysis of IL-17 family cytokines was performed in H. pylori-infected and uninfected gastric biopsy specimens. IL-17C mRNA was upregulated approximately 4.5-fold in H. pylori-infected gastric biopsy specimens. This was confirmed by quantitative reverse transcriptase PCR in infected and uninfected gastric mucosa obtained from Bhutan and from the Dominican Republic. Immunohistochemical analysis showed that IL-17C expression in H. pylori-infected gastric biopsy specimens was predominantly localized to epithelial and chromogranin A-positive endocrine cells. IL-17C mRNA levels were also significantly greater among cagA-positive than cagA-negative H. pylori infections (P ϭ 0.012). In vitro studies confirmed an increase in IL-17C mRNA and protein levels in cells infected with cagA-positive infections compared to cells infected with either cagA-negative or cag pathogenicity island (PAI) mutant. Chemical inhibition of IB kinase (IKK), mitogen-activated protein extracellular signal-regulated kinase (MEK), and Jun N-terminal kinase (JNK) inhibited induction of IL-17C proteins in infected cells, whereas p38 inhibition had no effect on IL-17C protein secretion. In conclusion, H. pylori infection was associated with a significant increase in IL-17C expression in human gastric mucosa. The role of IL-17C in the pathogenesis of H. pyloriinduced diseases remains to be determined.

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Section: Discussionmentioning

confidence: 99%

Interleukin-17C in Human Helicobacter pylori Gastritis

et al. 2017

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“…In support of the anti‐inflammatory effect of CB 1 agonism, CB 1 ‐deficient mice are more susceptible to experimental colitis (44), and administration of AEA or FAAH to mice with trinitrobenzosulfonic acid–induced colitis decreases the inflammatory response (23, 27). Additionally, studies in explant human tissue treated with proinflammatory cytokines have shown that AEA appears to prevent inflammation of the epithelium measured by macroscopic and microscopic colitis scores and levels of matrix metalloproteinase activity (45, 46). The effect of 2‐AG in human colonic tissue has not been reported.…”

Section: Discussionmentioning

confidence: 99%

The role of CB ₁ in intestinal permeability and inflammation

et al. 2017

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The endocannabinoid system has previously been shown to play a role in the permeability and inflammatory response of the human gut. The goal of our study was to determine the effects of endogenous anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) on the permeability and inflammatory response of intestinal epithelium under normal, inflammatory, and hypoxic conditions. Human intestinal mucosa was modeled using Caco-2 cells. Human tissue was collected from planned colorectal resections. Accumulation of AEA and 2-AG was achieved by inhibiting their metabolizing enzymes URB597 (a fatty acid amide hydrolase inhibitor) and JZL184 (a monoacylglycerol lipase inhibitor). Inflammation and ischemia were simulated with TNF-α and IFN-γ and oxygen deprivation. Permeability changes were measured by transepithelial electrical resistance. The role of the CB receptor was explored using CB-knockdown (CBKd) intestinal epithelial cells. Endocannabinoid levels were measured using liquid chromatography-mass spectrometry. Cytokine secretion was measured using multiplex and ELISA. URB597 and JZL184 caused a concentration-dependent increase in permeability CB ( < 0.0001) and decreased cytokine production. Basolateral application of JZL184 decreased permeability CB ( < 0.0001). URB597 and JZL184 increased the enhanced (worsened) permeability caused by inflammation and hypoxia ( < 0.0001 and < 0.05). CBKd cells showed reduced permeability response to inflammation ( < 0.01) but not hypoxia. 2-AG levels were increased in response to inflammation and hypoxia in Caco-2 cells. In human mucosal tissue, inflammation increased the secretion of granulocyte macrophage-colony stimulating factor, IL-12, -13, and -15, which was prevented with treatment with URB597 and JZL184, and was inhibited by a CB antagonist. The results of this study show that endogenous AEA and 2-AG production and CB activation play a key modulatory roles in normal intestinal mucosa permeability and in inflammatory and hypoxic conditions.-Karwad, M. A., Couch, D. G., Theophilidou, E., Sarmad, S., Barrett, D. A., Larvin, M., Wright, K. L., Lund, J. N., O'Sullivan, S. E. The role of CB in intestinal permeability and inflammation.

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“…CBD restored the increased permeability induced by EDTA or cytokines in a cell culture model of intestinal permeability (Alhamoruni et al 2010(Alhamoruni et al , 2012, counteracted reactive enteric gliosis (De Filippis et al 2011), induced autophagy in the intestinal epithelium (Koay et al 2014), reduced the expression of S100B and iNOS proteins in IBD patients' biopsies (De Filippis et al 2011), and attenuated the ability of IL-17A to elicit mucosal damage in a human colonic explant model (Harvey et al 2014). In vivo, CBD, given intraperitoneally, was effective in experimental models of colitis Jamontt et al 2010) and normalized the hypermotility associated with intestinal inflammation .…”

Section: Role Of Endocannabinoids In Bladder Functionmentioning

confidence: 99%

Endocannabinoids

2015

Handbook of Experimental Pharmacology

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Interleukin 17A evoked mucosal damage is attenuated by cannabidiol and anandamide in a human colonic explant model

Cited by 30 publications

References 53 publications

Interleukin-17C in Human Helicobacter pylori Gastritis

Interleukin-17C in Human Helicobacter pylori Gastritis

The role of CB ₁ in intestinal permeability and inflammation

Endocannabinoids

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Interleukin 17A evoked mucosal damage is attenuated by cannabidiol and anandamide in a human colonic explant model

Cited by 30 publications

References 53 publications

Interleukin-17C in Human Helicobacter pylori Gastritis

Interleukin-17C in Human Helicobacter pylori Gastritis

The role of CB 1 in intestinal permeability and inflammation

Endocannabinoids

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Resources

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The role of CB ₁ in intestinal permeability and inflammation