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Open AccessArticle

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

1
Department of Women, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, 80138 Naples, Italy
2
Department of Haematology, Bambino Gesù Hospital, 00165 Rome, Italy
3
Department of Experimental Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(5), 1049; https://doi.org/10.3390/ijms20051049
Received: 21 December 2018 / Revised: 21 February 2019 / Accepted: 22 February 2019 / Published: 28 February 2019
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. View Full-Text
Keywords: immune thrombocytopenia; mesenchymal stromal cells; cannabinoid receptor 2; dexamethasone immune thrombocytopenia; mesenchymal stromal cells; cannabinoid receptor 2; dexamethasone
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MDPI and ACS Style

Rossi, F.; Tortora, C.; Palumbo, G.; Punzo, F.; Argenziano, M.; Casale, M.; Di Paola, A.; Locatelli, F.; Perrotta, S. CB2 Receptor Stimulation and Dexamethasone Restore the Anti-Inflammatory and Immune-Regulatory Properties of Mesenchymal Stromal Cells of Children with Immune Thrombocytopenia. Int. J. Mol. Sci. 2019, 20, 1049. https://doi.org/10.3390/ijms20051049

AMA Style

Rossi F, Tortora C, Palumbo G, Punzo F, Argenziano M, Casale M, Di Paola A, Locatelli F, Perrotta S. CB2 Receptor Stimulation and Dexamethasone Restore the Anti-Inflammatory and Immune-Regulatory Properties of Mesenchymal Stromal Cells of Children with Immune Thrombocytopenia. International Journal of Molecular Sciences. 2019; 20(5):1049. https://doi.org/10.3390/ijms20051049

Chicago/Turabian Style

Rossi, Francesca; Tortora, Chiara; Palumbo, Giuseppe; Punzo, Francesca; Argenziano, Maura; Casale, Maddalena; Di Paola, Alessandra; Locatelli, Franco; Perrotta, Silverio. 2019. "CB2 Receptor Stimulation and Dexamethasone Restore the Anti-Inflammatory and Immune-Regulatory Properties of Mesenchymal Stromal Cells of Children with Immune Thrombocytopenia" Int. J. Mol. Sci. 20, no. 5: 1049. https://doi.org/10.3390/ijms20051049

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