Gender dependent importance of IRAK-1 in dextran sulfate sodium induced colitis.
Toll-like receptor (TLR) signaling is important for the induction of pro-inflammatory cytokines and interferon (IFN)-inducible genes in response to bacterial and viral challenge. Interleukin-1 receptor-associated kinase-1 (IRAK-1) is a signaling kinase situated downstream of the adapter protein myeloid differentiation factor 88 (MyD88) in the TLR intracellular signaling cascade and is required for normal signal transduction through this pathway. We investigated the importance of IRAK-1 in intestinal inflammation by using the dextran sulfate sodium (DSS)-colitis model. We show that IRAK-1 deficient mice are protected against systemic signs of inflammation, i.e., weight loss and spleen enlargement compared to wild-type controls irrespective of gender. However, IRAK-1(-/y) males but not IRAK-1(-/-) females display significant protection against colitis and thymic atrophy compared to wild-type mice. Our results indicate a gender specific effect of IRAK-1 in the DSS-induced colitis, an interesting finding since the Irak-1 gene is located on the X-chromosome and several inflammatory diseases have a gender dependent incidence.
Berglund
Martin
M
Dept. of Microbiology and Immunology, Institute of Biomedicine, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden. martin.berglund@immuno.gu.se
Thomas
James A
JA
Fredin
Maria Fritsch
MF
Melgar
Silvia
S
Hörnquist
Elisabeth H
EH
Hultgren
Olof H
OH
D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D003106:Colon / Q000378:metabolism / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012737:Sex Factors; D013950:Thymus Gland / Q000473:pathology / Q000502:physiology; D014960:X Chromosome / Q000235:genetics*
D007371:Interferon-gamma; D016264:Dextran Sulfate; D053592:Interleukin-1 Receptor-Associated Kinases; C507769:Irak1 protein, mouse