title: Inflammatory cytokine TSLP stimulates platelet secretion and potentiates platelet aggregation via a TSLPR-dependent PI3K/Akt signaling pathway.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.forename: Jiangchuan
authors.initials: J
authors.lastname: Dong
authors.affiliation: Department of emergency, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Jangchuan
authors.initials: J
authors.lastname: Dong
authors.forename: Jing
authors.initials: J
authors.lastname: Lin
authors.forename: Boyuan
authors.initials: B
authors.lastname: Wang
authors.forename: Shaolin
authors.initials: S
authors.lastname: He
authors.forename: Chun
authors.initials: C
authors.lastname: Wu
authors.forename: Kishan Kumar
authors.initials: KK
authors.lastname: Kushwaha
authors.forename: Nilesh
authors.initials: N
authors.lastname: Mohabeer
authors.forename: Yousu
authors.initials: Y
authors.lastname: Su
authors.forename: Hongcheng
authors.initials: H
authors.lastname: Fang
authors.forename: Kai
authors.initials: K
authors.lastname: Huang
authors.forename: Dazhu
authors.initials: D
authors.lastname: Li
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002341:Carotid Artery Thrombosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D002712:Chlorides / Q000633:toxicity; D002867:Chromones / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology*; D004195:Disease Models, Animal; D005290:Ferric Compounds / Q000633:toxicity; D006801:Humans; D007136:Immunoglobulins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009025:Morpholines / Q000494:pharmacology; D019007:P-Selectin / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D018121:Receptors, Cytokine / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D000077191:Wortmannin; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D000730:Androstadienes; D002712:Chlorides; D002867:Chromones; D016207:Cytokines; D005290:Ferric Compounds; D007136:Immunoglobulins; D009025:Morpholines; D019007:P-Selectin; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D051057:Proto-Oncogene Proteins c-akt; D018121:Receptors, Cytokine; D000077191:Wortmannin; D000094632:Thymic Stromal Lymphopoietin; C410591:Tslpr protein, mouse; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C024555:ferric chloride