Activation of TLR2 and TLR4 by minimally modified low-density lipoprotein in human macrophages and monocytes triggers the inflammatory response

Toll-Like Receptor Signaling in Burn Wound Healing and Scarring

“…17 Extracellular HMGB1 under the highly oxidizing conditions of burns is expected to be in the C23-C45 disulfide form, which activates TLR4 to induce cytokines. 18 In addition, oxidized lipoproteins can stimulate TLR2 and TLR4, resulting in inflammation, 19 suggesting that oxidized macromolecules in burn tissue may activate this inflammatory pathway.…”

Small Dense LDL Enhances THP-1 Macrophage Foam Cell Formation

“…This type of LDL is undoubtedly important in initiating the earliest steps of atherosclerosis. Recently, it has reported that activation of TLR4 by mmLDL in human macrophages and monocytes triggers an inflammatory response 23,24) . We demonstrated that sd-LDL-induced LOX-1 expression, was suppressed when TLR4 was inhibited.…”

The Innate Immune Response Mediated by TLRs in Atherosclerosis

“…Similarly, it has been shown that oxLDL, which can induce foam cell transformation, can increase TLR2 and TLR4 transcript expression (Holvoet et al, 2006). Surprisingly, mmLDL induces mRNA synthesis of IL-10 ( Bae et al, 2009) and the secretion of this cytokine in monocytes and macrophages (Chávez-Sánchez et al, 2010b), indicating that the activation of TLR2 and TLR4 also initiates regulatory mechanisms, including the production of anti-inflammatory cytokines such as IL-10 (Liew et al, 2005). Endogenous ligands have been associated with atherosclerosis in recent studies, including elevated serum amyloid A , which can predict cardiovascular events (Kosuge et al, 2007) and has been postulated as a shared mediator of inflammation and cardiovascular disease ( Wilson et al, 2008).…”

“…For example, Chávez-Sánchez et al used copper-modified LDL whereas Miller et al used LDL modified by fibroblasts that overexpressed 15-lipoxygenase. mmLDL has also been shown to activate TLR2 and induce the secretion of IL-1 , IL-6, and TNF-in human monocytes and macrophages (Chávez-Sánchez et al, 2010a, Chávez-Sánchez et al, 2010b. Moreover, the stimulation of monocytes with mmLDL causes a redistribution of CD14 and TLR4 on the cell surface, as well as the colocalization of CD14 and TLR4.…”

“…However, it has been shown that mmLDL induces secretion of pro-inflammatory cytokines, such as IL-1 , IL-6, and TNF-, in human monocytes and macrophages through CD14 (Chávez-Sánchez et al, 2010a, Chávez-Sánchez et al, 2010b, which is corroborated by the fact that the blockade of CD14 with anti-CD14 antibodies significantly reduces the concentration of pro-inflammatory cytokines, including IL-1 and IL-6, produced by macrophages in response to oxLDL (Pasini et al, 2007). The stimulation of human monocytes and macrophages with mmLDL induces the secretion of IL-1 , IL-6, and TNFthrough a TLR4-dependent mechanism (Chávez-Sánchez et al, 2010a, Chávez-Sánchez et al, 2010b, which is similar to the mechanism by which end products of LDL glycosylation lead to the production of TNF- (Hodgkinson et al, 2008a). Another study showed that mmLDL induces the secretion of MIP-2 in mice and that this secretion is TLR4/MyD88 dependent in mouse macrophages, whereas the secretion of MCP-1, TNF-, and IL-6 was shown to be independent of TLR4/MyD88 (Miller et al, 2005).…”