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

• Main Authors: Jangchuan Dong, Jing Lin, Boyuan Wang, Shaolin He, Chun Wu, Kishan Kumar Kushwaha, Nilesh Mohabeer, Yousu Su, Hongcheng Fang, Kai Huang, Dazhu Li
• Format: Article
• Language: English
• Published: Cell Physiol Biochem Press GmbH & Co KG 2015-01-01
• Series: Cellular Physiology and Biochemistry
• Subjects: Thymic stromal lymphopoietin; Platelet activation; Thrombus formation; PI3K/Akt signaling
• Online Access: http://www.karger.com/Article/FullText/369684
• ISSN: 1015-8987; 1421-9778

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.