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CB2 Receptor Stimulation and Dexamethasone Restore the Anti-Inflammatory and Immune-Regulatory Properties of Mesenchymal Stromal Cells of Children with Immune Thrombocytopenia.

Abstract
Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by antibody-mediated platelet destruction, with a complex and unclear pathogenesis. The impaired immunosuppressive capacity of mesenchymal stromal cells in ITP patients (ITP-MSCs) might play a role in the development of the disease. Correcting the MSC defects could represent an alternative therapeutic approach for ITP. High-dose dexamethasone (HD-Dexa) is the mainstay of the ITP therapeutic regimen, although it has several side effects. We previously demonstrated a role for cannabinoid receptor 2 (CB₂) as a mediator of anti-inflammatory and immunoregulatory properties of human MSCs. We analyzed the effects of CB₂ stimulation, with the selective agonist JWH-133, and of Dexa alone and in combination on ITP-MSC survival and immunosuppressive capacity. We provided new insights into the pathogenesis of ITP, suggesting CB₂ receptor involvement in the impairment of ITP-MSC function and confirming MSCs as responsive cellular targets of Dexa. Moreover, we demonstrated that CB₂ stimulation and Dexa attenuate apoptosis, via Bcl2 signaling, and restore the immune-modulatory properties of MSCs derived from ITP patients. These data suggest the possibility of using Dexa in combination with JWH-133 in ITP, reducing its dose and side effects but maintaining its therapeutic benefits.
AuthorsFrancesca Rossi, Chiara Tortora, Giuseppe Palumbo, Francesca Punzo, Maura Argenziano, Maddalena Casale, Alessandra Di Paola, Franco Locatelli, Silverio Perrotta
JournalInternational journal of molecular sciences (Int J Mol Sci) Vol. 20 Issue 5 (Feb 28 2019) ISSN: 1422-0067 [Electronic] Switzerland
PMID30823385 (Publication Type: Journal Article)
Chemical References
  • Anti-Inflammatory Agents
  • Cannabinoids
  • Receptor, Cannabinoid, CB2
  • Dexamethasone
  • 1,1-dimethylbutyl-1-deoxy-Delta(9)-THC
Topics
  • Anti-Inflammatory Agents (pharmacology)
  • Apoptosis
  • Cannabinoids (pharmacology)
  • Cells, Cultured
  • Child
  • Dexamethasone (pharmacology)
  • Female
  • Humans
  • Male
  • Mesenchymal Stem Cells (drug effects, immunology)
  • Purpura, Thrombocytopenic, Idiopathic (immunology)
  • Receptor, Cannabinoid, CB2 (agonists)

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