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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

Nyckelord

Animals

Colitis

chemically induced

genetics

pathology

Colon

metabolism

pathology

Dextran Sulfate

toxicity

Female

Interferon-gamma

metabolism

Interleukin-1 Receptor-Associated Kinases

genetics

physiology

Male

Mice

Mice

Inbred C57BL

Mice

Knockout

Sex Factors

Thymus Gland

pathology

physiology

X Chromosome

genetics

Medicine

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)