LINKING OXIDATIVE STRESS TO INFLAMMATION: TOLL-LIKE RECEPTORS

Injury caused by oxidative stress occurs in many clinical scenarios involving ischemia and reperfusion such as organ transplantation, hemorrhagic shock (HS), myocardial infarction and cerebral vascular accidents. Activation of the immune system as a result of disturbances in the redox state of cells appears to contribute to tissue and organ damage in these conditions. The link between oxidative stress and inflammatory pathways is poorly understood. Recently, Toll like receptors (TLRs) have been shown to mediate the inflammatory response seen in experimental ischemia and reperfusion (I/R). The TLR family of receptors involved in alerting the innate immune system of danger appears to be activated by damage associated molecular pattern molecules (DAMPs) that are released during condition of oxidative stress. In this review, we will examine the role of TLRs in various experimental models of oxidative stress such as HS and I/R. We will also report on potential DAMPs that may interact with TLRs in mediating injury. Finally, potential mechanisms by which reactive oxygen species from NADPH oxidase can signal the commencement of inflammatory pathways through TLRs will be explored.