The Expression and Functions of Toll-Like Receptors in Atherosclerosis

Abstract

Inflammation drives atherosclerosis. Both immune and resident vascular cell types are involved in the development of atherosclerotic lesions. The phenotype and function of these cells are key in determining the development of lesions. Toll-like receptors are the most characterised innate immune receptors and are responsible for the recognition of exogenous conserved motifs on pathogens, and, potentially, some endogenous molecules. Both endogenous and exogenous TLR agonists may be present in atherosclerotic plaques. Engagement of toll-like receptors on immune and resident vascular cells can affect atherogenesis as signalling downstream of these receptors can elicit proinflammatory cytokine release, lipid uptake, and foam cell formation and activate cells of the adaptive immune system. In this paper, we will describe the expression of TLRs on immune and resident vascular cells, highlight the TLR ligands that may act through TLRs on these cells, and discuss the consequences of TLR activation in atherosclerosis.

IL-1R–Associated Kinase-1 Mediates Protein Kinase Cδ-Induced IL-1β Production in Monocytes

“…Therefore, TLR4 may regulate IL-1b production through the conventional TLR/IL-1R pathway that may be independent of PKCd. Usually Pam3CSK4-induced IL-1b production is dependent on the TLR2 pathway whereas TLR4 mediates LPS-induced responses (57). Although our results demonstrate that PMA-induced increases in secreted IL-1b production are dependent on TLR2 and TLR4, PMA-induced TLR4 expression was unaffected by rottlerin.…”

Toll-like Receptors in the Vascular System: Sensing the Dangers Within

“…Further implicating the contribution of TLRs to atherosclerosis pathogenesis is the knowledge that oxidized lipoproteins are DAMPs that can activate TLR signaling (Miller, 2005). TLRs have been conclusively linked with the initiation of atherosclerosis, including being expressed on local vascular cells and recruited immune cells (Cole et al, 2010). Moreover, TLRs contribute to the progression of atherosclerosis, including being expressed in atherosclerotic lesions (Edfeldt et al, 2002) and contributing to matrix degradation (Monaco et al, 2009) and plaque destabilization (Ishibashi et al, 2013).…”

Developmental Onset of Bilirubin-induced Neurotoxicity Involves Toll-like Receptor 2-dependent Signaling in Humanized UDP-glucuronosyltransferase1 Mice

“…HSPs are predominantly intracellular molecules and are rapidly released following cell death (28). Recently, HSPs were implicated in modulating immune responses by interaction with TLRs as damage-associated molecular patterns (29,30). The association of HSP27 with cell injury and innate immunity prompted us to examine the role of TLR in response to bilirubin toxicity during neonatal brain development.…”