The role of aryl hydrocarbon receptor in interleukin-23-dependent restoration of interleukin-22 following ethanol exposure and burn injury Journal Article

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Authors: Rendon, J. L.; Li, X; Brubaker, A. L.; Kovacs, E. J.; Gamelli, R. L.; Choudhry, M. A.
Article Title: The role of aryl hydrocarbon receptor in interleukin-23-dependent restoration of interleukin-22 following ethanol exposure and burn injury
Abstract: OBJECTIVE: T-helper (Th)-17 lymphocytes play a crucial role in maintenance and regulation of gut immunity. Our laboratory has demonstrated that acute ethanol (EtOH) exposure before burn injury results in intestinal T cell suppression and enhanced bacterial translocation. BACKGROUND: To extend these studies, we examined the effects of EtOH exposure and burn injury on Th17 responses within intestinal lymphoid Peyer's patches (PP). We further investigated whether restitution of interleukin (IL)-23 enhances PP cell IL-17 and IL-22 after EtOH and burn injury. METHODS: Male mice, approximately 25 g, were gavaged with EtOH (2.9 mg/kg) before receiving an approximately 12.5% total body surface area full thickness burn. One day postinjury, PP mixed cells were cultured in the presence of plate-bound anti-CD3/soluble anti-CD28 in the presence or absence of IL-23 for 48 hours. Supernatants were harvested for IL-17 and IL-22 levels. RESULTS: When combined with EtOH intoxication, burn injury significantly decreased IL-17 and IL-22, as compared with sham injury. IL-23 treatment successfully increased levels of IL-22 but not IL-17. This restoration was prevented when PP cells were treated with CH-223191, an aryl hydrocarbon receptor inhibitor. To further delineate the mechanism of differential IL-17 and IL-22 suppression, PP cells were treated with phorbol 12-myristate 13-acetate (PMA) and ionomycin, which signal via protein kinase C (PKC) and calcium flux. Treatment with PMA and ionomycin significantly prevented the decrease in IL-17 but not IL-22 after EtOH exposure and burn injury. CONCLUSIONS: These findings suggest that IL-23-mediated restoration of IL-22 is aryl hydrocarbon receptor dependent, whereas IL-17 requires activation of protein kinase C and intracellular calcium signaling.
Journal Title: Annals of Surgery
Volume: 259
Issue: 3
ISSN: 1528-1140; 0003-4932
Publisher: Unknown  
Journal Place: United States
Date Published: 2014
Start Page: 582
End Page: 590
Language: eng
DOI/URL:

10.1097/SLA.0b013e3182a626f2
Notes: LR: 20141112; GR: F30 AA020167/AA/NIAAA NIH HHS/United States; GR: F30AA020167/AA/NIAAA NIH HHS/United States; GR: R01 AA015731/AA/NIAAA NIH HHS/United States; GR: R01AA015731/AA/NIAAA NIH HHS/United States; GR: R01AA015731-04S1/AA/NIAAA NIH HHS/United States; GR: T32AA013527/AA/NIAAA NIH HHS/United States; JID: 0372354; 0 (Interleukin-23); 0 (Interleukins); 0 (Receptors, Aryl Hydrocarbon); 0 (interleukin-22); 3K9958V90M (Ethanol); NIHMS550723; OID: NLM: NIHMS550723; OID: NLM: PMC3925750; ppublish