Low-dose ionizing radiation attenuates mast cell migration through suppression of monocyte chemoattractant protein-1 (MCP-1) expression by Nr4a2

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.

Keywords:

• Low-dose ionizing radiation
• mast cell migration
• transcription factor
• Nr4a2
• chemotactic cytokine
• MCP-1

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Additional information

Funding

This work was supported by the Ministry of Trade, Industry and Energy [MOTIE], Republic of Korea under Grant [number 20131610101840].

Notes on contributors

Chin-Hee Song

Chin-Hee Song obtained Ph.D. in biological science & biotechnology, Chonnam National University, Korea and was a researcher in Low-dose Radiation Research Team at KHNP-RHI. Now, she is a researcher in Healthcare Innovation Park, Seoul National University Bundang Hospital, Korea.

Hae Mi Joo

Hae Mi Joo obtained her master degree in School of Pharmacy, Sungkyunkwan University, Korea and is a researcher in Low-dose Radiation Research Team at KHNP-RHI.

So Hyun Han

So Hyun Han obtained her master degree in Department of Biological Sciences, Konkuk University, Korea and is a researcher in Low-dose Radiation Research Team at KHNP-RHI.

Jeong-In Kim

Jeong-In Kim complete his Ph.D. in the Department of Nuclear Engineering, Hanyang University, Korea and works as a health physics expert in Radiation Emergency Medical Team at KHNP-RHI.

Seon Young Nam

Seon Young Nam, Ph.D. in pharmacology, leads the Low-dose Radiation Research Team at KHNP-RHI. Her main research interests are the understanding of biological effect of low-dose ionizing radiation (LDIR) and the development of LDIR-specific biomarkers.

Ji Young Kim

Ji Young Kim obtained Ph.D. and followed as a research professor in School of Medicine, Sungkyunkwan University, Korea and currently, is a principal researcher in Low-dose Radiation Research Team at KHNP-RHI.