CB2 and TRPV1 receptors in inflammatory state of macrophages from sickle cell anemia pediatric/young adults

Abstract Sickle Cell Disease (SCD) is a monogenic disorder characterized by the production of abnormal hemoglobin. Polymerization of HbS causes sickling of red blood cells (RBCs) evidenced by acute adverse events and persistent inflammatory state, vasculopathy and organ damage. Sickled RBCs cause an...

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Main Authors: Giuseppe Di Feo, Giulia Giliberti, Deeksha Rana-Seyfert, Maria Maddalena Marrapodi, Maddalena Casale, Shakeel Ahmed, Silverio Perrotta, Francesca Rossi, Domenico Roberti, Alessandra Di Paola
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Language:English
Published: Nature Portfolio 2025-08-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-15028-2
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author Giuseppe Di Feo
Giulia Giliberti
Deeksha Rana-Seyfert
Maria Maddalena Marrapodi
Maddalena Casale
Shakeel Ahmed
Silverio Perrotta
Francesca Rossi
Domenico Roberti
Alessandra Di Paola
author_facet Giuseppe Di Feo
Giulia Giliberti
Deeksha Rana-Seyfert
Maria Maddalena Marrapodi
Maddalena Casale
Shakeel Ahmed
Silverio Perrotta
Francesca Rossi
Domenico Roberti
Alessandra Di Paola
author_sort Giuseppe Di Feo
collection DOAJ
description Abstract Sickle Cell Disease (SCD) is a monogenic disorder characterized by the production of abnormal hemoglobin. Polymerization of HbS causes sickling of red blood cells (RBCs) evidenced by acute adverse events and persistent inflammatory state, vasculopathy and organ damage. Sickled RBCs cause an anemic condition and vaso-occlusive crisis which trigger leukocytes, endothelial cells, and platelets. Due to these events, SCD patients unveiled an elevated level of pro-inflammatory cytokines, which contribute to the ongoing inflammatory state, oxidative stress, and other severe complications. SCD patients also experience neuropathic, inflammatory, and nociceptive pain. The discovery of novel therapeutic approaches and targets to counteract and manage inflammation in SCD are needed. Our study aimed to better understand the role of macrophages in SCD inflammation by first investigating their phenotype and then studying the iron metabolism involvement in the inflammatory processes. Therefore, given the importance to find novel therapeutic approach to contain and manage inflammation in these patients, and considering the role of CB2 and TRPV1 in this process, we decided to investigate the expression of these receptors and the effects of their stimulation on inflammatory state in SCD macrophages.
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spelling doaj-art-26eb7378992e4a138e53bd30826af79f2025-08-20T03:43:02ZengNature PortfolioScientific Reports2045-23222025-08-0115111610.1038/s41598-025-15028-2CB2 and TRPV1 receptors in inflammatory state of macrophages from sickle cell anemia pediatric/young adultsGiuseppe Di Feo0Giulia Giliberti1Deeksha Rana-Seyfert2Maria Maddalena Marrapodi3Maddalena Casale4Shakeel Ahmed5Silverio Perrotta6Francesca Rossi7Domenico Roberti8Alessandra Di Paola9Department of Woman, Child and General and Specialist Surgery, University of Campania “Luigi Vanvitelli”Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”Department of Woman, Child and General and Specialist Surgery, University of Campania “Luigi Vanvitelli”Department of Woman, Child and General and Specialist Surgery, University of Campania “Luigi Vanvitelli”Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”Department of Woman, Child and General and Specialist Surgery, University of Campania “Luigi Vanvitelli”Department of Woman, Child and General and Specialist Surgery, University of Campania “Luigi Vanvitelli”Department of Woman, Child and General and Specialist Surgery, University of Campania “Luigi Vanvitelli”Department of Woman, Child and General and Specialist Surgery, University of Campania “Luigi Vanvitelli”Abstract Sickle Cell Disease (SCD) is a monogenic disorder characterized by the production of abnormal hemoglobin. Polymerization of HbS causes sickling of red blood cells (RBCs) evidenced by acute adverse events and persistent inflammatory state, vasculopathy and organ damage. Sickled RBCs cause an anemic condition and vaso-occlusive crisis which trigger leukocytes, endothelial cells, and platelets. Due to these events, SCD patients unveiled an elevated level of pro-inflammatory cytokines, which contribute to the ongoing inflammatory state, oxidative stress, and other severe complications. SCD patients also experience neuropathic, inflammatory, and nociceptive pain. The discovery of novel therapeutic approaches and targets to counteract and manage inflammation in SCD are needed. Our study aimed to better understand the role of macrophages in SCD inflammation by first investigating their phenotype and then studying the iron metabolism involvement in the inflammatory processes. Therefore, given the importance to find novel therapeutic approach to contain and manage inflammation in these patients, and considering the role of CB2 and TRPV1 in this process, we decided to investigate the expression of these receptors and the effects of their stimulation on inflammatory state in SCD macrophages.https://doi.org/10.1038/s41598-025-15028-2Sickle cell anemiaInflammationMacrophage polarizationIron metabolismEndocannabinoid/Endovanilloid system
spellingShingle Giuseppe Di Feo
Giulia Giliberti
Deeksha Rana-Seyfert
Maria Maddalena Marrapodi
Maddalena Casale
Shakeel Ahmed
Silverio Perrotta
Francesca Rossi
Domenico Roberti
Alessandra Di Paola
CB2 and TRPV1 receptors in inflammatory state of macrophages from sickle cell anemia pediatric/young adults
Scientific Reports
Sickle cell anemia
Inflammation
Macrophage polarization
Iron metabolism
Endocannabinoid/Endovanilloid system
title CB2 and TRPV1 receptors in inflammatory state of macrophages from sickle cell anemia pediatric/young adults
title_full CB2 and TRPV1 receptors in inflammatory state of macrophages from sickle cell anemia pediatric/young adults
title_fullStr CB2 and TRPV1 receptors in inflammatory state of macrophages from sickle cell anemia pediatric/young adults
title_full_unstemmed CB2 and TRPV1 receptors in inflammatory state of macrophages from sickle cell anemia pediatric/young adults
title_short CB2 and TRPV1 receptors in inflammatory state of macrophages from sickle cell anemia pediatric/young adults
title_sort cb2 and trpv1 receptors in inflammatory state of macrophages from sickle cell anemia pediatric young adults
topic Sickle cell anemia
Inflammation
Macrophage polarization
Iron metabolism
Endocannabinoid/Endovanilloid system
url https://doi.org/10.1038/s41598-025-15028-2
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