Toll-like Receptor 2 Is Essential for the Sensing of Oxidants during Inflammation
| Autor: | Mark J. Paul-Clark, Jane Mitchell, Bernhard Ryffel, Shiranee Sriskandan, Valérie F. J. Quesniaux, Laura Moreno, Lucy Bailey, Rosalinda Sorrentino, Shaun K. McMaster |
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| Přispěvatelé: | Department of Critical Care (DCC), Imperial College London-National Heart and Lung Institute [UK], Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2009 |
| Předmět: |
Critical Care and Intensive Care Medicine
Mice 0302 clinical medicine MESH: Oxidants MESH: Animals MESH: Bronchitis 0303 health sciences Toll-like receptor MESH: Oxidative Stress medicine.diagnostic_test Kinase Smoking MESH: Toll-Like Receptor 2 MESH: Enzyme-Linked Immunosorbent Assay Oxidants 3. Good health Blot 030220 oncology & carcinogenesis [SDV.IMM]Life Sciences [q-bio]/Immunology medicine.symptom Pulmonary and Respiratory Medicine MESH: Smoking MESH: Peritonitis Blotting Western Enzyme-Linked Immunosorbent Assay Inflammation Peritonitis 03 medical and health sciences C. Critical Care Western blot MESH: Mice Inbred C57BL medicine Animals Humans MESH: Blotting Western Interleukin 8 Bronchitis MESH: Mice 030304 developmental biology MESH: Humans business.industry Molecular biology Toll-Like Receptor 2 Mice Inbred C57BL stomatognathic diseases Disease Models Animal Oxidative Stress TLR2 Immunology TLR4 MESH: Disease Models Animal business |
| Zdroj: | American Journal of Respiratory and Critical Care Medicine American Journal of Respiratory and Critical Care Medicine, American Thoracic Society, 2009, 179 (4), pp.299-306. ⟨10.1164/rccm.200707-1019OC⟩ |
| ISSN: | 1535-4970 1073-449X |
| DOI: | 10.1164/rccm.200707-1019oc |
| Popis: | International audience; RATIONALE: The mechanisms by which oxidants are sensed by cells and cause inflammation are not well understood. OBJECTIVES: This study aimed to determine how cells "sense" soluble oxidants and how this is translated into an inflammatory reaction. METHODS: Monocytes, macrophages, or HEK293 cells (stably transfected with human Toll-like receptor [TLR]2, TLR2/1, TLR2/6, or TLR4/MD2-CD14) were used. CXC ligand-8 (CXCL8) levels were measured using ELISA. Phosphorylated IL-1 receptor-associated kinase 1 levels were measured using Western blot. TLR2(-/-) and TLR4(-/-) mice were challenged with oxidants, and inflammation was measured by monitoring cell infiltration and KC levels. MEASUREMENTS AND MAIN RESULTS: Oxidants evoked the release of CXCL8 from monocytes/macrophages; this was abrogated by pretreatment with N-acetylcysteine or binding antibodies to TLR2 and was associated with the rapid phosphorylation of IL-1 receptor-associated kinase 1. Oxidants added to HEK293 cells transfected with TLR2, TLR1/2, or TLR2/6 but not TLR4/MD2-CD14 or control HEK nulls resulted in the release of CXCL8. Oxidant challenge delivered intraperitoneally (2-24 hours) or by inhalation to the lungs (3 days) resulted in a robust inflammation in wild-type mice. TLR2(-/-) mice did not respond to oxidant challenge in either model. TLR4(-/-) mice responded as wild-type mice to oxidants at 2 hours but as TLR2(-/-) mice at later time points. CONCLUSIONS: Oxidant-TLR2 interactions provide a signal that initiates the inflammatory response. |
| Databáze: | OpenAIRE |
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