title: IL-1 receptor-associated kinase M downregulates DSS-induced colitis.
abstract: BACKGROUND
  Ulcerative colitis is associated with increased colon permeability resulting in bacterial translocation into the lamina propria. We investigate the importance of the Toll-like receptor (TLR) regulating protein IL-1 receptor-associated kinase M (IRAK-M) using the erosive dextran sulfate sodium (DSS)-induced model of colitis.
  
  
  METHODS
  IRAK-M-competent and -incompetent mice were treated with 3% DSS for 5 days followed by 2 days of regular drinking water. Clinical signs of disease were followed for 7 days. At day 7 the mice were sacrificed and plasma and tissue were collected for histopathological examination and analyses of the production of cytokines and chemokines as well as expression of T-cell transcription factors.
  
  
  RESULTS
  At day 7 IRAK-M-deficient mice display a reduced total body weight (77.1 ± 2.1 versus 88.5 ± 2.0, *P = 0.002) and an increased macroscopical (2.7 ± 0.2 versus 1.6 ± 0.1, *P = 0.002) and histopathological (6.0 ± 0 versus 3.3 ± 0.5, *P = < 0.001) colon score compared to wildtype mice. Furthermore, IRAK-M-deficient mice have increased colon mRNA expression of proinflammatory cytokines and increased tumor necrosis factor concentrations (41.1 ± 13.5 versus 12.8 ± 2.0 pg/mL, *P = 0.010) in plasma.
  
  
  CONCLUSIONS
  This is the first report examining the role of IRAK-M in colitis. We find that IRAK-M is of critical importance in downregulating induction and progression of DSS colitis, and thereby suggesting that IRAK-M might be a target for future interventional therapies.
authors.affiliation: Department of Microbiology and Immunology, Institute of Biomedicine, The Sahlgrenska Academy at Göteborg University, Sweden. martin.berglund@immuno.gu.se
authors.forename: Martin
authors.initials: M
authors.lastname: Berglund
authors.forename: Silvia
authors.initials: S
authors.lastname: Melgar
authors.forename: Koichi S
authors.initials: KS
authors.lastname: Kobayashi
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: Elisabeth Hultgren
authors.initials: EH
authors.lastname: Hörnquist
authors.forename: Olof H
authors.initials: OH
authors.lastname: Hultgren
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D016264:Dextran Sulfate / Q000633:toxicity*; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D053592:Interleukin-1 Receptor-Associated Kinases / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D016264:Dextran Sulfate; D053592:Interleukin-1 Receptor-Associated Kinases; C507772:Irak3 protein, mouse