| Autor: |
Paul-Clark MJ, McMaster SK, Sorrentino R, Sriskandan S, Bailey LK, Moreno L, Ryffel B, Quesniaux VF, Mitchell JA, Paul-Clark, Mark J, McMaster, Shaun K, Sorrentino, Rosalinda, Sriskandan, Shiranee, Bailey, Lucy K, Moreno, Laura, Ryffel, Bernhard, Quesniaux, Valerie F, Mitchell, Jane A |
| Zdroj: |
American Journal of Respiratory & Critical Care Medicine; Feb2009, Vol. 179 Issue 4, p299-306, 8p |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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