Annals of Surgery

Skip Navigation LinksHome > March 2014 - Volume 259 - Issue 3 > The Role of Aryl Hydrocarbon Receptor in Interleukin-23-Depe...
Annals of Surgery:
doi: 10.1097/SLA.0b013e3182a626f2
Original Articles

The Role of Aryl Hydrocarbon Receptor in Interleukin-23-Dependent Restoration of Interleukin-22 Following Ethanol Exposure and Burn Injury

Rendon, Juan L. PhD; Li, Xiaoling MD; Brubaker, Aleah L. PhD; Kovacs, Elizabeth J. PhD; Gamelli, Richard L. MD; Choudhry, Mashkoor A. PhD

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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.

© 2014 by Lippincott Williams & Wilkins.


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