Toll-like receptor 2 is essential for the sensing of oxidants during inflammation.

Abstract:

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.

authors

Paul-Clark MJ,McMaster SK,Sorrentino R,Sriskandan S,Bailey LK,Moreno L,Ryffel B,Quesniaux VF,Mitchell JA

doi

10.1164/rccm.200707-1019OC

subject

Has Abstract

pub_date

2009-02-15 00:00:00

pages

299-306

issue

4

eissn

1073-449X

issn

1535-4970

pii

200707-1019OC

journal_volume

179

pub_type

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