Divergence of apoptosis-inducing and preventing signals in bacteria-faced macrophages through myeloid differentiation factor 88 and IL-1 receptor-associated kinase members
| Autor: | Oliver Mannel, Percy Schröttner, Klaus Ruckdeschel |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Lipopolysaccharides
Programmed cell death Proteasome Endopeptidase Complex Cell Survival Leupeptins Fas-Associated Death Domain Protein Immunology Apoptosis Cysteine Proteinase Inhibitors Models Biological Cell Line Mice Bacterial Proteins Multienzyme Complexes Immunology and Allergy Macrophage Cytotoxic T cell Animals FADD Receptors Immunologic Transcription factor Cells Cultured Death domain Adaptor Proteins Signal Transducing Yersinia enterocolitica TNF Receptor-Associated Factor 6 Caspase 8 biology Macrophages NF-kappa B Proteins Antigens Differentiation Caspase 9 Cell biology Cysteine Endopeptidases Interleukin-1 Receptor-Associated Kinases Caspases Myeloid Differentiation Factor 88 Cancer research biology.protein Carrier Proteins Protein Kinases Signal Transduction |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 168(9) |
| ISSN: | 0022-1767 |
| Popis: | The induction of apoptosis in host cells is a common strategy by which pathogenic bacteria interfere with the host immune response. The Yersinia enterocolitica outer protein P (YopP) inhibits activation of transcription factor NF-κB in macrophages, which suppresses NF-κB-dependent antiapoptotic activities. The simultaneous initiation of proapoptotic signaling by yersiniae infection or LPS treatment results in macrophage apoptosis. In this study, we used YopP as a tool to dissect survival- and death-inducing pathways in bacteria-faced macrophages. We cotransfected J774A.1 macrophages with expression plasmids for YopP and dominant-negative mutants of signal transmitters of the NF-κB cascade downstream from the LPS receptor complex. Dominant-negative myeloid differentiation factor 88 (MyD88) or IL-1R-associated kinase (IRAK) 2 diminished LPS-induced apoptosis in YopP-transfected macrophages, suggesting implication of MyD88 and IRAK2 in signaling cell death. In contrast, dominant-negative IRAK1 and TNFR-associated factor 6 (TRAF6) did not provide protection, but augmented LPS-mediated apoptosis in the absence of YopP, which indicates roles of IRAK1 and TRAF6 in the antiapoptotic signal relay of the NF-κB cascade. The distinct functions of IRAK members in macrophage survival were reflected by opposing effects of dominant-negative IRAK1 and IRAK2 on Y. enterocolitica-mediated apoptosis. Yersiniae- and LPS-dependent cell death were substantially attenuated by a specific caspase-8 inhibitory peptide or by dominant negative Fas-associated death domain protein (FADD). This suggests, that Yersinia-induced apoptosis involves a proapoptotic signal relay through MyD88 and IRAK2, which potentially targets the Fas-associated death domain protein/caspase-8 apoptotic pathway, whereas IRAK1 and TRAF6 counteract the bacteria-induced cytotoxic response by signaling macrophage survival. |
| Databáze: | OpenAIRE |
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