| First Author | Paul-Clark MJ | Year | 2009 |
| Journal | Am J Respir Crit Care Med | Volume | 179 |
| Issue | 4 | Pages | 299-306 |
| PubMed ID | 19011150 | Mgi Jnum | J:165007 |
| Mgi Id | MGI:4835875 | Doi | 10.1164/rccm.200707-1019OC |
| Citation | Paul-Clark MJ, et al. (2009) Toll-like receptor 2 is essential for the sensing of oxidants during inflammation. Am J Respir Crit Care Med 179(4):299-306 |
| abstractText | 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. |
