title: Increased expression of MAIL, a cytokine-associated nuclear protein, in the prodromal stage of black walnut-induced laminitis.
abstract: BACKGROUND
  The mediators and signalling cascades important in the initiation of laminitis remain unclear. We therefore wanted to explore the genes and overall signalling mechanisms that play an important role in the developmental stage of laminitis.
  
  
  OBJECTIVE
  To use a broad genomic screening technique to identify novel genes that are differentially regulated in the equine lamellae during the developmental period of laminitis.
  
  
  METHODS
  Differential mRNA display (DRD) was performed to discover regulated genes, and real-time quantitative polymerase chain reaction (RT-qPCR) was then used to evaluate lamellar mRNA levels of a regulated gene (MAIL) and mediators related to that gene (IL-1beta and IL-6) in control horses (n = 5) and horses administered black walnut extract (BWE; n = 5).
  
  
  RESULTS
  Using DRD, MAIL was identified as a regulated gene. RT-qPCR indicated a 4-fold increase in expression of the MAIL mRNA in BWE lamellae compared to controls. A 30-fold increase in IL-1beta, and a 160-fold difference in IL-6 mRNA expression was present in BWE lamellae. Differences in MAIL, IL-1beta and IL-6 mRNA expression were statistically significant between groups (P < 0.05).
  
  
  CONCLUSIONS
  The data strongly support a role for inflammatory cytokines in the developmental stages of laminitis, possibly inducing the vascular and metabolic alterations reported to occur in the affected digit. These results potentially support the use of anti-inflammatory drugs in horses at risk of laminitis, and warrant further investigation of the link between systemic disease processes associated with laminitis and the reported digital inflammation.
authors.affiliation: Department of Veterinary Clinical Science, School of Veterinary Medicine, Louisiana State University, Baton Rouge Louisiana 70803, USA.
authors.forename: R W
authors.initials: RW
authors.lastname: Waguespack
authors.forename: R J
authors.initials: RJ
authors.lastname: Kemppainen
authors.forename: A
authors.initials: A
authors.lastname: Cochran
authors.forename: H C
authors.initials: HC
authors.lastname: Lin
authors.forename: J K
authors.initials: JK
authors.lastname: Belknap
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D018076:DNA, Complementary / Q000502:physiology; D005260:Female; D005534:Foot Diseases / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control / Q000662:veterinary*; D005552:Forelimb / Q000378:metabolism; D005786:Gene Expression Regulation; D006724:Hoof and Claw / Q000378:metabolism*; D006734:Horse Diseases / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D006736:Horses; D020672:I-kappa B Proteins; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control / Q000662:veterinary; D007375:Interleukin-1 / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D031324:Juglans / Q000009:adverse effects; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction / Q000662:veterinary; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000893:Anti-Inflammatory Agents; D018076:DNA, Complementary; D020672:I-kappa B Proteins; D007375:Interleukin-1; D015850:Interleukin-6; C417234:NFKBIZ protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger