IL-1 receptor-associated kinase M downregulates DSS-induced colitis.
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.
Berglund
Martin
M
Department of Microbiology and Immunology, Institute of Biomedicine, The Sahlgrenska Academy at Göteborg University, Sweden. martin.berglund@immuno.gu.se
Melgar
Silvia
S
Kobayashi
Koichi S
KS
Flavell
Richard A
RA
Hörnquist
Elisabeth Hultgren
EH
Hultgren
Olof H
OH
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
D016207:Cytokines; D012333:RNA, Messenger; D016264:Dextran Sulfate; D053592:Interleukin-1 Receptor-Associated Kinases; C507772:Irak3 protein, mouse