| | |  | | | | Record from Web of Science® | | | | | | |
| Impaired cytokine signaling in mice lacking the IL-1 receptor-associated kinase |
|
|
| Author(s): Thomas JA, Allen JL, Tsen M, Dubnicoff T, Danao J, Liao XC, Cao ZD, Wasserman SA |
| Source: JOURNAL OF IMMUNOLOGY Volume: 163 Issue: 2 Pages: 978-984 Published: JUL 15 1999 |
| Times Cited: 159 References: 50 |
| Abstract: Stimulation of the type 1 IL-1R (IL-1R1) and the IL-18R by their cognate ligands induces recruitment of the IL-1R-associated kinase (IRAK), Activation of IRAK leads in turn to nuclear translocation of NF-kappa B, which directs expression of innate and adaptive immune response genes. To study IRAK function in cytokine signaling, we generated cells and mice lacking the IRAK protein. IRAK-deficient fibroblasts show diminished activation of NF-kappa B when stimulated with IL-1, Immune effector cells without IRAK exhibit a defective IFN-gamma response to costimulation with IL-18, Furthermore, mice lacking the Irak gene demonstrate an attenuated response to injected IL-1, Deletion of Irak, however, does not affect the ability of mice to develop delayed-type hypersensitivity or dear infection with the intracellular parasite, Listeria monocytogenes. These results demonstrate that although IRAK participates in IL-1 and IL-18 signal transduction, residual cytokine responsiveness operates through an IRAK-independent pathway. |
| Document Type: Article |
| Language: English |
| Reprint Address: Thomas, JA (reprint author), Univ Texas, SW Med Ctr, Dept Pediat, 5323 Harry Hines Blvd,Room NA5-320A, Dallas, TX 75235 USA |
Addresses:
1. Univ Texas, SW Med Ctr, Dept Pediat, Dallas, TX 75235 USA
2. Univ Texas, SW Med Ctr, Dept Mol Biol & Oncol, Dallas, TX 75235 USA
3. Tularik Inc, S San Francisco, CA 94080 USA |
| Publisher: AMER ASSOC IMMUNOLOGISTS, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA |
| Subject Category: Immunology |
| IDS Number: 215AY |
| ISSN: 0022-1767 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |