Toll‐like receptor‐4 and mitogen‐activated protein kinase signal system are involved in activation of dendritic cells in patients with acute coronary syndrome

Abstract

Summary Atherosclerosis is an inflammatory disease in which dendritic cells have been suggested to play an essential role. The underlying signalling mechanisms are unknown thus far. The family of Toll‐like receptors (TLRs) initiates innate immune responses, and Toll‐like receptor‐4 (TLR4) has been considered to be an important player in the initiation and progression of atherosclerotic disease. The highly conserved mitogen‐activated protein kinase (MAPK) family is one of the major kinase families that regulate cells by transducing extracellular into cellular responses. Three important members of this family are the extracellular signal‐regulated kinase (ERK), p38, and c‐Jun N‐terminal kinase (JNK). The aim of the study was to investigate the expression of TLR4 and MAPK families on dendritic cells (DC) in patients with coronary arteriosclerosis disease. We have examined the expression of TLR4 protein and mRNA by flow cytometry and real‐time quantitative reverse transcription polymerase chain reaction (RT–PCR). In addition, the expression of MAPK family proteins have been determined by Western blot analysis. We examined the expression level of CD80 to value the maturation state of DC. We compared the levels of cytokines in DC in response to lipopolysaccharide (LPS). The results showed that the expression of TLR4 and MAPK families are increased in the patients with acute coronary syndrome (ACS), compared with it in the patients with stable angina and controls. DC in ACS are activated evaluated by its mature marker and cytokine secreting responding to LPS. We suggest that TLR4 and MAPK families maybe involved in activation of circulating DC of ACS patients.

Kruppel-Like Factor 2 Regulates Dendritic Cell Activation in Patients with Acute Coronary Syndrome

“…Our study, as well as others, has indicated that TLR4 plays a key role in the activation of DCs [7,16]. Furthermore, surface molecules responsible for inducing T-cell activation such as the co-stimulatory molecules CD80 and CD86, or the major histocompatability complex (MHC) class I and II antigens were involved too [17].…”

“…Once sufficiently activated, vascular DCs may present autoantigens to T cells and initiate inflammatory responses directly in the arterial wall, and thus lead to the inflammatory process of atherosclerosis [6]. We had shown in our previous study that DCs were activated in ACS via the Toll-like receptor4/MAPKsignal pathway [7]. Although there are reports of various studies about their inflammatory mechanisms in AS, DC activation still remains largely unknown.…”

Dendritic cells and their role in atherogenesis

“…15,115,116 TLR4 which has a central role in the initiation and progression of atherosclerosis is expressed by DCs in the arterial wall. 117,118 Modified autoantigens, such as oxLDL, heat-shock proteins (HSPs) and fragments of bacteria, such as lipopolysaccharides, are recognized by TLR4, followed by the activation of the subsequent signaling cascade. 15,[117][118][119][120][121][122][123] TLR2 may contribute to atherogenesis, possibly activating DCs due to the presence of Chlamydia pneumoniae in atherosclerotic lesions.…”

Dendritic Cells in Cardiovascular Diseases

“…It is assumed that December 17, 2013 these DCs are involved in postischemic short-term cytoprotective responses through TLR2 and TLR4 stimulation by tissue-released DAMP. 77 Maekawa and coworkers, 78 on the contrary, demonstrated in a murine myocardial infarction model (left coronary artery ligation) that deletion of interleukin-1 receptor-associated kinase-4 , a downstream effector of the TLR/MyD88 axis, had beneficial effects on survival and function after myocardial infarction by blunting DC mobilization into the heart and attenuating local inflammatory processes. Of note, cardiomyocytes and residential macrophages also express TLR2 and TLR4 and are able to respond to endogenous DAMPs, thereby contributing to inflammatory processes after myocardial infarction.…”