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.

• Authors: Juan L Rendon, Xiaoling Li, Aleah L Brubaker, Elizabeth J Kovacs, Richard L Gamelli, Mashkoor A Choudhry
• Journal: Annals of surgery (Ann Surg) Vol. 259 Issue 3 Pg. 582-90 (Mar 2014) ISSN: 1528-1140 [Electronic] United States
• PMID: 23989051 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-23
• Interleukins
• Receptors, Aryl Hydrocarbon
• Ethanol

Topics

• Animals
• Burns (immunology, metabolism, pathology)
• Cells, Cultured
• Disease Models, Animal
• Enzyme-Linked Immunosorbent Assay
• Ethanol (pharmacology)
• Flow Cytometry
• Immunity, Cellular
• Interleukin-23 (drug effects, immunology, metabolism)
• Interleukins (immunology, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Receptors, Aryl Hydrocarbon (physiology)
• Signal Transduction (drug effects)
• Th17 Cells (immunology, metabolism, pathology)
• Interleukin-22