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Low-dose ionizing radiation attenuates mast cell migration through suppression of monocyte chemoattractant protein-1
Chin-Hee Song1, Hae Mi Joo1, So Hyun Han1
1Low-dose Radiation Research Team, Radiation Health Institute, Korea Hydro & Nuclear Power Co., Ltd, Seoul, Republic of Korea.
Abstract:
Purpose: The aim of this study was to investigate whether low-dose ionizing radiation attenuates mast cell migration by modulating migration-associated signaling pathways and the expression of chemotactic cytokines.Materials and methods: IgE-sensitized RBL-2H3 mast cells were exposed with ionizing radiation at 0.01, 0.05, 0.1, or 0.5 Gy using a 137Cs γ-irradiator and stimulated with 2,4-dinitrophenol-human serum albumin. Cell migration was determined using a transwell assay system, F-actin distribution using Alex Fluor 488-conjugated phalloidin, expression of various signaling proteins by Western blotting, mRNA expression by RT-PCR.Results: Low-dose ionizing radiation significantly suppressed mast cell migration induced by IgE-mediated mast cell activation. Furthermore, low-dose ionizing radiation altered cell morphology, as reflected by changes in F-actin distribution, and inhibited the activation of PI3K, Btk, Rac1, and Cdc42. These effects were mediated by Nr4a2, an immune-modulating factor. Knockdown of Nr4a2 reduced mast cell migration, inhibited the PI3K and Btk signaling pathways, and reduced expression of the chemotactic cytokine monocyte chemoattractant protein-1 (MCP-1). We further demonstrated that direct blockade of MCP-1 using neutralizing antibodies inhibits mast cell migration.Conclusion: Low-dose ionizing radiation inhibits mast cell migration through the regulation production of MCP-1 by Nr4a2 in the activated mast cell system.
Insights
Low-dose ionizing radiation effectively inhibits mast cell migration by modulating Nr4a2 and reducing monocyte chemoattractant protein-1 (MCP-1) production. This finding offers insights into radiation
Area of Science:
- Immunology
- Radiation Biology
- Cell Signaling
Background:
- Mast cells play a crucial role in allergic inflammation and immune responses.
- Mast cell migration is a key process in inflammatory conditions.
- Understanding factors that modulate mast cell migration is vital for therapeutic development.
Purpose of the Study:
- To investigate the effect of low-dose ionizing radiation on mast cell migration.
- To elucidate the underlying molecular mechanisms, including signaling pathways and cytokine expression.
Main Methods:
- Utilized IgE-sensitized RBL-2H3 mast cells exposed to varying doses of ionizing radiation (0.01–0.5 Gy).
- Assessed cell migration using transwell assays, F-actin distribution, Western blotting for protein expression, and RT-PCR for mRNA.
- Investigated the role of Nr4a2 and monocyte chemoattractant protein-1 (MCP-1) in radiation-modulated mast cell migration.
Main Results:
- Low-dose ionizing radiation significantly suppressed IgE-mediated mast cell migration.
- Radiation altered cell morphology and inhibited key signaling proteins (PI3K, Btk, Rac1, Cdc42) via Nr4a2.
- Nr4a2 knockdown reduced migration and inhibited PI3K/Btk signaling, decreasing MCP-1 expression; MCP-1 blockade also inhibited migration.
Conclusions:
- Low-dose ionizing radiation inhibits mast cell migration by regulating Nr4a2-mediated production of MCP-1.
- This study reveals a novel mechanism by which radiation modulates immune cell function.
- Findings suggest potential therapeutic applications of low-dose radiation in managing mast cell-driven inflammatory diseases.
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