Journal Article

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

Casale, Maddalena, Perrotta, Silverio, Giliberti, Giulia, Ahmed, Shakeel, Rossi, Francesca, Roberti, Domenico, Di Paola, Alessandra, Rana-Seyfert, Deeksha, Marrapodi, Maria Maddalena, Di Feo, Giuseppe

2025

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/250/256 / 631/80 / 631/80/85 / 692/699/1541 / 692/699/1541/4036 / Adolescent / Adult / Agonists / Anemia / Anemia, Sickle Cell - metabolism / Anemia, Sickle Cell - pathology / Blood platelets / Capsaicin receptors / Child / Cytokines / Cytokines - metabolism / Endocannabinoid/Endovanilloid system / Endothelial cells / Erythrocytes / Female / Genotype & phenotype / Hemoglobin / Homeostasis / Humanities and Social Sciences / Humans / Inflammation / Inflammation - metabolism / Inflammation - pathology / Iron / Iron - metabolism / Leukocytes / Macrophage polarization / Macrophages / Macrophages - metabolism / Macrophages - pathology / Male / Marketing / Metabolism / multidisciplinary / Oxidative stress / Pain / Pain perception / Pediatrics / Phenotypes / Polymerization / Protein expression / Receptor, Cannabinoid, CB2 - genetics / Receptor, Cannabinoid, CB2 - metabolism / Science / Science (multidisciplinary) / Sickle cell anemia / Sickle cell disease / TRPV Cation Channels - genetics / TRPV Cation Channels - metabolism / Tumor necrosis factor-TNF / Vascular diseases / Young Adult / Young adults