IL-17A Facilitates Platelet Function through the ERK2 Signaling Pathway in Patients with Acute Coronary Syndrome

Zhang, Shuang; Yuan, Jing; Yu, Miao; Hong, Fan; Guo, Zhangqiang; Yang, Rui; Guo, Hao; Liao, Yuhua; Wang, Min

doi:10.1371/journal.pone.0040641

Cited by 45 publications

(45 citation statements)

References 22 publications

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“…Additionally, they are central players in vascular inflammation processes via the recruitment of leukocytes, which leads to the progression of atherosclerosis and plaque destabilization [9]. Accumulating literature suggests a delicate role of cytokines in atherothrombosis, and members of the cytokine family have been shown to activate platelets via their receptors [10,11]. However, the exact signaling mechanisms of platelet activation by inflammatory cytokines remain unknown.…”

Section: Introductionmentioning

confidence: 99%

Inflammatory Cytokine TSLP Stimulates Platelet Secretion and Potentiates Platelet Aggregation via a TSLPR-Dependent PI3K/Akt Signaling Pathway

Dong

Lin

Wang

et al. 2015

Cell Physiol Biochem

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Aims: Thymic stromal lymphopoietin (TSLP) plays an important role in inflammatory diseases and is over-expressed in human atherosclerotic artery specimens. The present study investigated the role of TSLP in platelet activation and thrombosis models in vitro and in vivo, as well as the underlying mechanism and signaling pathway. Methods and Results: Western blotting and flow cytometry demonstrated that the TSLP receptor was expressed on murine platelets. According to flow cytometry, platelet stimulation with TSLP induced platelet degranulation and integrin αIIbβ3 activation. A TSLPR deficiency caused defective platelet aggregation, defective platelet secretion and markedly blunted thrombus growth in perfusion chambers at both low and high shear rates. TSLPR KO mice exhibited defective carotid artery thrombus formation after exposure to FeCl₃. TSLP increased Akt phosphorylation, an effect that was abrogated by the PI3K inhibitors wortmannin and LY294002. The PI3K inhibitors further diminished TSLP-induced platelet activation. TSLP-mediated platelet degranulation, integrin αIIbβ3 activation and Akt phosphorylation were blunted in platelets that lacked the TSLP receptor. Conclusion: This study demonstrated that the functional TSLPR was surface-expressed on murine platelets. The inflammatory cytokine TSLP triggered platelet activation and thrombus formation via TSLP-dependent PI3K/Akt signaling, which suggests an important role for TSLP in linking vascular inflammation and thrombo-occlusive diseases.

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Section: Introductionmentioning

confidence: 99%

Inflammatory Cytokine TSLP Stimulates Platelet Secretion and Potentiates Platelet Aggregation via a TSLPR-Dependent PI3K/Akt Signaling Pathway

Dong

Lin

Wang

et al. 2015

Cell Physiol Biochem

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“…Plaque rupture exposes thrombogenic components such as collagen, which could activate and link platelets, and the activated platelets may then release ADP to induce further platelet activation, ultimately leading to intravascular thrombus formation [1,2,3,23,24,25]. Many studies have demonstrated that platelets contribute to immunoreactivity and can be activated by certain inflammatory factors [4,5,6,27]. In a preliminary study, we showed that TSLP promotes inflammation in atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

Human Platelets Express Functional Thymic Stromal Lymphopoietin Receptors: a Potential Role in Platelet Activation in Acute Coronary Syndrome

Wang

Peng²,

Dong³

et al. 2013

Cell Physiol Biochem

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Background: Thymic stromal lymphopoietin (TSLP) has been shown to be expressed in various inflammatory tissues, such as human atherosclerotic plaques. Many types of myeloid cells involved in atherosclerosis, including mast cells, lymphocytes, dendritic cells and monocytes/macrophages, present TSLP receptors (TSLPR). However, it is unknown whether platelets, which also play important roles in atherothrombosis, express TSLPR. Methods and Results: We applied flow cytometry and western blotting to show that TSLPR was expressed on the surface of human platelets. Following the addition of TSLP to platelets, the expression of CD62P, CD63, PAC-1 and p-Akt as well as aggregation and ATP release were increased significantly. A TSLPR antibody and a PI3K (phosphatidylinositol 3-kinase) enzyme inhibitor (LY294002) significantly inhibited the platelet activation induced by TSLP. The expression of TSLPR, CD62P and CD63 and the increment of the expression of CD62P and CD63 induced by TSLP in the acute coronary syndrome (ACS) group were markedly higher than those in the control group and the stable angina pectoris (SAP) group. The expression and the increment of the expression of CD62P and CD63 induced by TSLP were positively correlated with the expression of TSLPR. Conclusion: Human platelets express functional TSLPR, which can be activated by TSLP to promote platelet activation. TSLP/TSLPR functions via activating the PI3K/AKT pathway, and this signalling pathway may be one of the mechanisms involved in thrombosis in ACS. In coronary disease patients, the determination of TSLPR in platelets may help to identify the risk of ACS.

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“…Besides platelet activation, the chronic inflammatory burden of psoriatic patients may also be the trigger for the development of CVD, with interleukin (IL)-12 and IL-17 implicated in the pathogenesis of both diseases[19-21]. Interestingly, IL-17 has recently been shown to facilitate platelet aggregation[22]. …”

Section: Introductionmentioning

confidence: 99%

Increased levels of circulating platelet-derived microparticles in psoriasis: Possible implications for the associated cardiovascular risk

Papadavid

Diamanti

Spathis

et al. 2016

WJC

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AIMTo evaluate platelet activation markers in psoriasis patients, compared to controls, and investigate their association with the inflammatory burden of psoriasis.METHODSForty psoriatic patients without cardiovascular disease, and 12 healthy controls were subjected to measurement of baseline platelet CD62P, CD63 and CD42b expression, platelet-leukocyte complexes, i.e., platelet-monocyte complexes (PMC), platelet-neutrophil complexes (PNC) and platelet-lymphocyte complexes, and concentrations of platelet-derived microparticles (PMPs) using flow cytometry. Both larger-size (0.5-0.9 μm) and smaller-size (< 0.5 μm) PMPs were determined. Serum interleukin (IL)-12 and IL-17 levels were also measured by enzyme-linked immunosorbent assay. The severity of psoriasis was evaluated by the Psoriasis Area Severity Index (PASI).RESULTSPMP concentrations were significantly higher in psoriasis patients than controls [mean ± standard error of mean (SEM): 22 ± 5/μL vs 11 ± 6/μL; P = 0.018), for both smaller-size (10 ± 2/μL vs 4 ± 2/μL; P = 0.033) and larger-size (12 ± 3/μL vs 6 ± 4/μL; P = 0.014) PMPs. Platelet CD62P, CD63 and CD42b expression and circulating PMC and PNC were similar between the two groups. Lower circulating PLC were observed in psoriasis patients compared to controls (mean ± SEM: 16% ± 3% vs 23% ± 6%; P = 0.047). Larger-size PMPs were related with IL-12 levels (P < 0.001) and smaller-size PMPs with both IL-12 and IL-17 levels (P < 0.001). Total PMPs also correlated with IL-12 (P < 0.001). CD63 expression was positively correlated with both IL-12 and IL-17 (P < 0.05). Increased PASI score was associated with increased levels of larger-size PMPs (r = 0.45; P = 0.011) and increased CD63 expression (r = 0.47; P < 0.01).CONCLUSIONPMPs, known to be predictive of cardiovascular outcomes, are increased in psoriasis patients, and associated with high inflammatory disease burden. Enhanced platelet activation may be the missing link leading to cardiovascular events in psoriatic patients.

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IL-17A Facilitates Platelet Function through the ERK2 Signaling Pathway in Patients with Acute Coronary Syndrome

Cited by 45 publications

References 22 publications

Inflammatory Cytokine TSLP Stimulates Platelet Secretion and Potentiates Platelet Aggregation via a TSLPR-Dependent PI3K/Akt Signaling Pathway

Inflammatory Cytokine TSLP Stimulates Platelet Secretion and Potentiates Platelet Aggregation via a TSLPR-Dependent PI3K/Akt Signaling Pathway

Human Platelets Express Functional Thymic Stromal Lymphopoietin Receptors: a Potential Role in Platelet Activation in Acute Coronary Syndrome

Increased levels of circulating platelet-derived microparticles in psoriasis: Possible implications for the associated cardiovascular risk

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