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.
authors.affiliation: From the Alcohol Research Program, Burn & Shock Trauma Research Institute, Department of Surgery and Department of Microbiology and Immunology, Cell Biology, Neurobiology & Anatomy Program, Loyola University Chicago Health Sciences Division, Maywood, IL.
authors.forename: Juan L
authors.initials: JL
authors.lastname: Rendon
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Li
authors.forename: Aleah L
authors.initials: AL
authors.lastname: Brubaker
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Kovacs
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gamelli
authors.forename: Mashkoor A
authors.initials: MA
authors.lastname: Choudhry
mesh_terms: D000818:Animals; D002056:Burns / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D000431:Ethanol / Q000494:pharmacology*; D005434:Flow Cytometry; D007111:Immunity, Cellular; D053759:Interleukin-23 / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D007378:Interleukins / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018336:Receptors, Aryl Hydrocarbon / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000097043:Interleukin-22
chemical_list: D000431:Ethanol; D053759:Interleukin-23; D007378:Interleukins; D018336:Receptors, Aryl Hydrocarbon; D000097043:Interleukin-22