PMID- 31287373 OWN - NLM STAT- MEDLINE DCOM- 20200131 LR - 20200131 IS - 1362-3095 (Electronic) IS - 0955-3002 (Linking) VI - 95 IP - 11 DP - 2019 Nov TI - Low-dose ionizing radiation attenuates mast cell migration through suppression of monocyte chemoattractant protein-1 (MCP-1) expression by Nr4a2. PG - 1498-1506 LID - 10.1080/09553002.2019.1642535 [doi] AB - 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 (137)Cs gamma-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. FAU - Song, Chin-Hee AU - Song CH AD - Low-dose Radiation Research Team, Radiation Health Institute, Korea Hydro & Nuclear Power Co., Ltd, Seoul, Republic of Korea. FAU - Joo, Hae Mi AU - Joo HM AD - Low-dose Radiation Research Team, Radiation Health Institute, Korea Hydro & Nuclear Power Co., Ltd, Seoul, Republic of Korea. FAU - Han, So Hyun AU - Han SH AD - Low-dose Radiation Research Team, Radiation Health Institute, Korea Hydro & Nuclear Power Co., Ltd, Seoul, Republic of Korea. FAU - Kim, Jeong-In AU - Kim JI AD - Radiation Emergency Medical Team, Radiation Health Institute, Korea Hydro & Nuclear Power Co., Ltd, Seoul, Republic of Korea. FAU - Nam, Seon Young AU - Nam SY AD - Low-dose Radiation Research Team, Radiation Health Institute, Korea Hydro & Nuclear Power Co., Ltd, Seoul, Republic of Korea. FAU - Kim, Ji Young AU - Kim JY AD - Low-dose Radiation Research Team, Radiation Health Institute, Korea Hydro & Nuclear Power Co., Ltd, Seoul, Republic of Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190809 PL - England TA - Int J Radiat Biol JT - International journal of radiation biology JID - 8809243 RN - 0 (Actins) RN - 0 (Ccl2 protein, rat) RN - 0 (Cesium Radioisotopes) RN - 0 (Chemokine CCL2) RN - 0 (Cytokines) RN - 0 (Nr4a2 protein, rat) RN - 0 (Nuclear Receptor Subfamily 4, Group A, Member 2) RN - 17466-45-4 (Phalloidine) RN - 4T2E65IAR7 (Cesium-137) SB - IM MH - Actins/metabolism MH - Animals MH - Cell Line, Tumor MH - Cell Movement/*radiation effects MH - Cesium Radioisotopes MH - Chemokine CCL2/*metabolism MH - Chemotaxis MH - Cytokines/metabolism MH - Gamma Rays MH - Gene Expression Profiling MH - Gene Expression Regulation MH - Mast Cells/cytology/*radiation effects MH - Nuclear Receptor Subfamily 4, Group A, Member 2/*metabolism MH - Phalloidine/metabolism MH - *RNA Interference MH - Rats MH - Signal Transduction OTO - NOTNLM OT - Low-dose ionizing radiation OT - MCP-1 OT - Nr4a2 OT - chemotactic cytokine OT - mast cell migration OT - transcription factor EDAT- 2019/07/10 06:00 MHDA- 2020/02/01 06:00 CRDT- 2019/07/10 06:00 PHST- 2019/07/10 06:00 [pubmed] PHST- 2020/02/01 06:00 [medline] PHST- 2019/07/10 06:00 [entrez] AID - 10.1080/09553002.2019.1642535 [doi] PST - ppublish SO - Int J Radiat Biol. 2019 Nov;95(11):1498-1506. doi: 10.1080/09553002.2019.1642535. Epub 2019 Aug 9.