TITLE

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

AUTHOR(S)
Dong, Jangchuan; Lin, Jing; Wang, Boyuan; He, Shaolin; Wu, Chun; Kushwaha, Kishan Kumar; Mohabeer, Nilesh; Su, Yousu; Fang, Hongcheng; Huang, Kai; Li, Dazhu
PUB. DATE
January 2015
SOURCE
Cellular Physiology & Biochemistry (Karger AG);Jan2015, Vol. 35 Issue 1, p160
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
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. © 2015 S. Karger AG, Basel
ACCESSION #
100439573

 

Related Articles

  • Murine allergic rhinitis and nasal Th2 activation are mediated via TSLP- and IL-33-signaling pathways. Shoko Akasaki; Kazufumi Matsushita; Yukinori Kato; Ayumi Fukuoka; Naruhito Iwasaki; Masakiyo Nakahira; Shigeharu Fujieda; Koubun Yasuda; Tomohiro Yoshimoto // International Immunology;Feb2016, Vol. 28 Issue 2, p65 

    Thymic stromal lymphopoietin (TSLP) and IL-33 are epithelium-derived proallergic cytokines that contribute to allergic diseases. Although the involvement of TSLP in allergic rhinitis (AR) is suggested, the exact role of TSLP in AR is poorly understood. Furthermore, the relative contribution of...

  • TSLP Directly Interacts with Skin-Homing Th2 Cells Highly Expressing its Receptor to Enhance IL-4 Production in Atopic Dermatitis. Tatsuno, Kazuki; Fujiyama, Toshiharu; Yamaguchi, Hayato; Waki, Michihiko; Tokura, Yoshiki // Journal of Investigative Dermatology;Dec2015, Vol. 135 Issue 12, p3017 

    Thymic stromal lymphopoietin (TSLP) is overtly expressed on skin lesions of atopic dermatitis (AD), and the initiative role of TSLP-activated DCs in AD has gained much attention in the past few years, while its actions on other immune cells such as T cells have been given less notice. We aimed...

  • A Potential Mechanism of High-Dose Ticagrelor in Modulating Platelet Activity and Atherosclerosis Mediated by Thymic Stromal Lymphopoietin Receptor. Mao, Yi; Peng, Yudong; Zeng, Qiutang; Cheng, Longxian; Wang, Boyuan; Mao, Xiaobo; Meng, Kai; Liu, Yuzhou; Lian, Yitian; Li, Dazhu // PLoS ONE;10/30/2015, Vol. 10 Issue 10, p1 

    Abnormal expression of thymic stromal lymphopoietin (TSLP) and its receptor (TSLPR) was found in patients with acute coronary syndrome. Ticagrelor, an oral platelet ADP P2Y12 receptor antagonist, is widely used in these patients. The aim of this study was to verify whether different doses of...

  • Interleukin 7 and thymic stromal lymphopoietin: from immunity to leukemia. Tal, Noa; Shochat, Chen; Geron, Ifat; Bercovich, Dani; Izraeli, Shai // Cellular & Molecular Life Sciences;Feb2014, Vol. 71 Issue 3, p365 

    Cancer is often caused by deregulation of normal developmental processes. Here, we review recent research on the aberrant activation of two hematopoietic cytokine receptors in acute lymphoid leukemias. Somatic events in the genes for thymic stromal lymphopoietin and Interleukin 7 receptors as...

  • Structural basis of the proinflammatory signaling complex mediated by TSLP. Verstraete, Kenneth; van Schie, Loes; Vyncke, Laurens; Bloch, Yehudi; Tavernier, Jan; Pauwels, Ewald; Peelman, Frank; Savvides, Savvas N // Nature Structural & Molecular Biology;Apr2014, Vol. 21 Issue 4, p375 

    Thymic stromal lymphopoietin (TSLP), a cytokine produced by epithelial cells at barrier surfaces, is pivotal for the development of widespread chronic inflammatory disorders such as asthma and atopic dermatitis. The structure of the mouse TSLP-mediated signaling complex reveals how TSLP...

  • Alteration of Cytokine Production during Visceral Larva Migrans by Toxascaris leonina in Mice. Shin Ae Kang; Mi-Kyung Park; Min Kyoung Cho; Hak Sun Yu // Korean Journal of Parasitology;Oct2013, Vol. 51 Issue 5, p583 

    To determine alteration of immune responses during visceral larva migrans (VLM) caused by Toxascaris leonina at several time points, we experimentally infected mice with embryonated eggs of T. leonina and measured T-helper (Th) cell-related serial cytokine production after infection. At day 5...

  • The role of basophils and proallergic cytokines, TSLP and IL-33, in cutaneously sensitized food allergy. Muto, Taichiro; Fukuoka, Ayumi; Kabashima, Kenji; Ziegler, Steven F.; Nakanishi, Kenji; Matsushita, Kazufumi; Yoshimoto, Tomohiro // International Immunology;Oct2014, Vol. 26 Issue 10, p539 

    The roles of basophils, TSLP and IL-33 in food allergy following epicutaneous sensitizationCutaneous sensitization with a food antigen before its consumption elicits the development of food allergy. Here, we report the site- and stage-dependent roles of basophils and proallergic cytokines,...

  • Interleukin-25 induces type 2 cytokine production in a steroid-resistant interleukin-17RB+ myeloid population that exacerbates asthmatic pathology. Petersen, Bryan C; Budelsky, Alison L; Baptist, Alan P; Schaller, Matthew A; Lukacs, Nicholas W // Nature Medicine;May2012, Vol. 18 Issue 5, p751 

    Interleukin-25 (IL-25) is a cytokine associated with allergy and asthma that functions to promote type 2 immune responses at mucosal epithelial surfaces and serves to protect against helminth parasitic infections in the intestinal tract. This study identifies the IL-25 receptor, IL-17RB, as a...

  • A novel role for STAT5 in DC Controlling the Th2 response. Tormo, Aurélie Jeanne; Gauchat, Jean-François // JAK-STAT;Oct-Dec2013, Vol. 2 Issue 4, pe25352-1 

    Dendritic cells (DC) play a key role in immunity by recognizing and presenting antigens. Cytokines and cytokine-activated transcription factors are fundamental in the regulation of the DC differentiation and their functions. While the role of STAT3 in DC development is well established, the...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics