Cited by 26Platelet Disorders and TreatmentsBlood Coagulation and Thrombosis MechanismsVenous Thromboembolism Diagnosis and Management

IL-9 promotes the development of deep venous thrombosis by facilitating platelet function

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Feng, Yuqian, Yu, Miao, Zhu, Feng, Zhang, Shaoshao, Ding, Peiwu, Wang, Min·2018·Thrombosis and Haemostasis

Abstract

The development of deep venous thrombosis (DVT) is a sterile inflammatory process related to cytokines, such as interleukin (IL)-6 or IL-17. IL-9 is a cytokine involved in many inflammatory diseases, including cystic fibrosis, ulcerative colitis, psoriasis and psoriatic arthritis. However, it remains unknown whether IL-9 is related to DVT. In this study, we characterized the role and mechanism of IL-9 in DVT. Analysis of the data of patients with and without DVT revealed that stasis, venous surgery as well as elevated IL-9 and sP-selectin levels were related to the development of DVT. We also showed for the first time that IL-9 receptor was expressed in mouse platelets, and it dramatically promoted the aggregation rate and expression of P-selectin (CD62P) in the presence of adenosine diphosphate, but otherwise exhibited no effect on platelets. This study also revealed that Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signalling pathway, not phosphoinositide 3-kinase/AKT pathway, was involved in the process. We also showed in a mouse model of stasis that the thrombus size (weight and length) and CD62P expression in the thrombus were higher and lower in the IL-9 group and IL-9 antibody group, respectively, than in the control group. All these findings indicated that IL-9 facilitated platelet function through the JAK2/STAT3 pathway, thus promoting the development of DVT.

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Research works printed but not linked: 20

  1. Law Y, Chan YC, Cheng SWK. Epidemiological updates of venous thromboembolism in a Chinese population. Asian J Surg 2018;41 (02):176-182
  2. Dewyer NA, El-Sayed OM, Luke CE, et al. Divergent effects of Tlr9 deletion in experimental late venous thrombosis resolution and vein wall injury. Thromb Haemost 2015;114(05):1028-1037
  3. Zhang S, Yuan J, Yu M, et al. IL-17A facilitates platelet function through the ERK2 signaling pathway in patients with acute coronary syndrome. PLoS One 2012;7(07):e40641
  4. Yuan J, Ding PW, Yu M, et al. IL-17 induces MPTP opening through ERK2 and P53 signaling pathway in human platelets. J Huazhong Univ Sci Technolog Med Sci 2015;35(05):679-683
  5. Nowak EC, Weaver CT, Turner H, et al. IL-9 as a mediator of Th17- driven inflammatory disease. J Exp Med 2009;206(08):1653-1660
  6. Singh TP, Schön MP, Wallbrecht K, Gruber-Wackernagel A, Wang XJ, Wolf P. Involvement of IL-9 in Th17-associated inflammation and angiogenesis of psoriasis. PLoS One 2013;8(01):e51752
  7. Han JS, Park TS, Cho SY, Joh JH, Ahn HJ. Increased mean platelet volume and mean platelet volume/platelet count ratio in Korean patients with deep vein thrombosis. Platelets 2013;24(08):590-593
  8. Panuganti S, Schlinker AC, Lindholm PF, Papoutsakis ET, Miller WM. Three-stage ex vivo expansion of high-ploidy megakaryo- cytic cells: toward large-scale platelet production. Tissue Eng Part A 2013;19(7-8):998-1014
  9. Simanek R, Vormittag R, Ay C, et al. High platelet count associated with venous thromboembolism in cancer patients: results from the Vienna Cancer and Thrombosis Study (CATS). J Thromb Hae- most 2010;8(01):114-120
  10. Zhang W, Tang T, Nie D, et al. IL-9 aggravates the development of atherosclerosis in ApoE-/-mice. Cardiovasc Res 2015;106(03): 453-464
  11. Mosevoll KA, Lindãs R, Tvedt THA, Bruserud Ø, Reikvam H. Altered plasma levels of cytokines, soluble adhesion molecules and matrix metalloproteases in venous thrombosis. Thromb Res 2015;136(01):30-39 12
  12. González-Ordóñez AJ, Fernández-Carreira JM, Fernández-Alvarez CR, et al. The concentrations of soluble vascular cell adhesion molecule-1 and lipids are independently associated with venous thromboembolism. Haematologica 2003;88(09):1035-1043 13
  13. Antonopoulos CN, Sfyroeras GS, Kakisis JD, Moulakakis KG, Liapis CD. The role of soluble P selectin in the diagnosis of venous thromboembolism. Thromb Res 2014;133(01):17-24
  14. Hou H, Ge Z, Ying P, et al. Biomarkers of deep venous thrombosis. J Thromb Thrombolysis 2012;34(03):335-346
  15. Vandy FC, Stabler C, Eliassen AM, et al. Soluble P-selectin for the diagnosis of lower extremity deep venous thrombosis. J Vasc Surg Venous Lymphat Disord 2013;1(02):117-1125
  16. Brill A, Fuchs TA, Chauhan AK, et al. von Willebrand factor- mediated platelet adhesion is critical for deep vein thrombosis in mouse models. Blood 2011;117(04):1400-1407
  17. Demoulin JB, Van Snick J, Renauld JC. Interleukin-9 (IL-9) induces cell growth arrest associated with sustained signal transducer and activator of transcription activation in lymphoma cells overexpres- sing the IL-9 receptor. Cell Growth Differ 2001;12(03):169-174
  18. Lu WJ, Lin KC, Huang SY, et al. Role of a Janus kinase 2-dependent signaling pathway in platelet activation. Thromb Res 2014;133 (06):1088-1096
  19. Tibbles HE, Vassilev A, Wendorf H, et al. Role of a JAK3-dependent biochemical signaling pathway in platelet activation and aggre- gation. J Biol Chem 2001;276(21):17815-17822
  20. Holinstat M, Preininger AM, Milne SB, Hudson WJ, Brown HA, Hamm HE. Irreversible platelet activation requires protease- activated receptor 1-mediated signaling to phosphatidylinositol phosphates. Mol Pharmacol 2009;76(02):301-313

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Authors
Feng, Y., Yu, M., Zhu, F., Zhang, S., Ding, P., & Wang, M.
Affiliations
Wuhan Union Hospital (CN)
Venue
Thrombosis and Haemostasis
Published
2018-10-09
Volume
118
Issue
11
Pages
1885-1894
ISSN
  • 0340-6245 (ISSN-L)
  • 2567-689X
OpenAlex
W2898082547
Cited by
26
References
0
Citations by year
2025: 3 · 2024: 2 · 2023: 6 · 2022: 3 · 2021: 1 · 2020: 11
FWCI
2.15
Type
journal article
Language
en
Open access
Locations
  • Thrombosis and Haemostasis (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China (81370425)
Topics
  • Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
  • Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
  • Health Sciences › Medicine › Internal Medicine › Venous Thromboembolism Diagnosis and Management
Keywords
IL-9, deep vein thrombosis, platelet function, platelet aggregation, P-selectin, IL-9 receptor, JAK2/STAT3 signaling, venous stasis, sterile inflammation, cytokines, thrombus formation
MeSH terms
Animals, Blood Platelets, Cells, Cultured, Humans, Male, Mice, Inbred BALB C, Platelet Aggregation, Signal Transduction, Interleukin-9, Disease Progression, P-Selectin, Antibodies, Blocking, Venous Thrombosis, STAT3 Transcription Factor, Mice, Janus Kinase 2, Receptors, Interleukin-9

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