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

**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

PMC · DOI: 10.1038/s41598-025-15028-2 · Scientific Reports · 2025-08-08

## TL;DR

This paper investigates the role of CB2 and TRPV1 receptors in the inflammatory state of macrophages in sickle cell anemia patients.

## Contribution

The study explores novel therapeutic targets (CB2 and TRPV1) for managing inflammation in sickle cell disease.

## Key findings

- SCD patients exhibit elevated pro-inflammatory cytokines and ongoing inflammation.
- CB2 and TRPV1 receptors are investigated for their potential role in modulating inflammation in SCD macrophages.

## 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.

The online version contains supplementary material available at 10.1038/s41598-025-15028-2.

## Linked entities

- **Proteins:** CNR2 (cannabinoid receptor 2), TRPV1 (transient receptor potential cation channel subfamily V member 1)
- **Diseases:** Sickle Cell Disease (MONDO:0011382), sickle cell anemia (MONDO:0011382)

## Full-text entities

- **Genes:** CNR2 (cannabinoid receptor 2) [NCBI Gene 1269] {aka CB-2, CB2, CX5}, TRPV1 (transient receptor potential cation channel subfamily V member 1) [NCBI Gene 7442] {aka VR1}
- **Diseases:** abnormal hemoglobin (MESH:D006445), pain (MESH:D010146), vaso-occlusive crisis (MESH:D001157), neuropathic (MESH:D009437), vasculopathy (MESH:D000090122), organ damage (MESH:D000092124), anemic condition (MESH:D020763), inflammation (MESH:D007249), monogenic disorder (MESH:D009358), nociceptive (MESH:D059226), SCD (MESH:D000755)
- **Chemicals:** iron (MESH:D007501)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12334692/full.md

## References

14 references — full list in the complete paper: https://tomesphere.com/paper/PMC12334692/full.md

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Source: https://tomesphere.com/paper/PMC12334692