An Essential Role of the NF-κB/Toll-Like Receptor Pathway in Induction of Inflammatory and Tissue-Repair Gene Expression by Necrotic Cells
| Autor: | David F. Carpio, Peter Bruzzo, Ruslan Medzhitov, Ming O. Li, Ye Zheng, Fateh Ouaaz, Veena M. Singh, Amer A. Beg |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Chemokine
Programmed cell death Necrosis Chemokine CXCL1 Toll-Like Receptor Pathway Immunology Apoptosis Receptors Cell Surface Inflammation Cell Line Mice medicine Animals Drosophila Proteins Immunology and Allergy Cells Cultured Wound Healing Membrane Glycoproteins biology Macrophages Interleukin-8 Toll-Like Receptors NF-kappa B Transcription Factor RelA Fibroblasts Embryo Mammalian Toll-Like Receptor 2 Cell biology Mice Inbred C57BL Gene Expression Regulation Cell culture biology.protein Cytokines Chemokines Inflammation Mediators medicine.symptom Signal transduction Chemokines CXC Interleukin-1 Signal Transduction |
| Zdroj: | The Journal of Immunology. 166:7128-7135 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Tissue damage induced by infection or injury can result in necrosis, a mode of cell death characterized by induction of an inflammatory response. In contrast, cells dying by apoptosis do not induce inflammation. However, the reasons for underlying differences between these two modes of cell death in inducing inflammation are not known. Here we show that necrotic cells, but not apoptotic cells, activate NF-κB and induce expression of genes involved in inflammatory and tissue-repair responses, including neutrophil-specific chemokine genes KC and macrophage-inflammatory protein-2, in viable fibroblasts and macrophages. Intriguingly, NF-κB activation by necrotic cells was dependent on Toll-like receptor 2, a signaling pathway that induces inflammation in response to microbial agents. These results have identified a novel mechanism by which cell necrosis, but not apoptosis, can induce expression of genes involved in inflammation and tissue-repair responses. Furthermore, these results also demonstrate that the NF-κB/Toll-like receptor 2 pathway can be activated both by exogenous microbial agents and endogenous inflammatory stimuli. |
| Databáze: | OpenAIRE |
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