Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function.
MyD88, originally isolated as a myeloid differentiation primary response gene, is shown to act as an adaptor in interleukin-1 (IL-1) signaling by interacting with both the IL-1 receptor complex and IL-1 receptor-associated kinase (IRAK). Mice generated by gene targeting to lack MyD88 have defects in T cell proliferation as well as induction of acute phase proteins and cytokines in response to IL-1. Increases in interferon-gamma production and natural killer cell activity in response to IL-18 are abrogated. In vivo Th1 response is also impaired. Furthermore, IL-18-induced activation of NF-kappaB and c-Jun N-terminal kinase (JNK) is blocked in MyD88-/- Th1-developing cells. Taken together, these results demonstrate that MyD88 is a critical component in the signaling cascade that is mediated by IL-1 receptor as well as IL-18 receptor.
Pubmed ID: 9697844 RIS Download
Adaptor Proteins, Signal Transducing | Animals | Antigens, Differentiation | COS Cells | Calcium-Calmodulin-Dependent Protein Kinases | Cells, Cultured | Cytokines | DNA | Enzyme Activation | Female | Gene Targeting | Humans | Interleukin-1 | Interleukin-18 | JNK Mitogen-Activated Protein Kinases | Male | Mice | Mice, Inbred C57BL | Mice, Knockout | Mitogen-Activated Protein Kinases | Myeloid Differentiation Factor 88 | NF-kappa B | Proteins | Receptors, Immunologic | Th1 Cells