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Nutlin-3a Inhibits the Production of CXCL10 by Ionizing Radiation in J774A.1 Murine Macrophages
Biomed Sci Letters 2024;30:341-348
Published online December 31, 2024;  https://doi.org/10.15616/BSL.2024.30.4.341
© 2024 The Korean Society For Biomedical Laboratory Sciences.

Ji An Seo1,§,*, Ji Sue Baik1,§,*, Song Mi Lee2,**, Shin Yeong Jun2,**, Jin Soo Kang2,***, Min Soo Seo2,***, Man Hee Rhee2,†,***, Moon-Taek Park1,†,****, and Sung Dae Kim2,†,***

1Research Center, Dongnam Institute of Radiological & Medical Sciences, Busan 46033, Korea
2Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Korea
Correspondence to: †Man Hee Rhee
Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 41566, Korea
Tel: +82-53-950-5957, Fax: +82-53-950-5954, E-mail: rheemh@knu.ac.kr, ORCID: https://orcid.org/0000-0002-3088-1318

Moon-Taek Park
Research Center, Dongnam Institute of Radiological & Medical Sciences, 40 Jwadong-gil, Jangan-eup, Gijang-gun, Busan 46033, Korea
Tel: +82-51-720-5141, Fax: +82-51-720-5992, E-mail: mtpark@dirams.re.kr, ORCID: https://orcid.org/0000-0001-7665-2265

Sung Dae Kim
Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 41566, Korea
Tel: +82-53-950-5958, Fax: +82-53-950-5954, E-mail: kim79sd@knu.ac.kr, ORCID: https://orcid.org/0000-0001-9891-8888

*Researcher, **Ungraduate student, ***Professor, ****Senior researcher.
§These authors contributed equally to this work.
Received September 4, 2024; Revised October 3, 2024; Accepted October 16, 2024.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
 Abstract
Nutlin-3a inhibits the interaction between p53, a tumor suppressor protein, and MDM2, an E3 ubiquitin ligase, thereby stabilizing and activating p53. Although the pathophysiological effects of Nutlin-3a, based on its activation of p53, have been documented, studies on its impacts on radiation-exposed macrophages remain sparse. This study explored the modulatory effect of Nutlin-3a on ionizing radiation (IR)-induced CXCL10 production in J774A.1 murine macrophages. Nutlin-3a reduces IR-induced CXCL10 production in these cells and also inhibits IR-induced p38 MAPK activation in the same macrophages. Moreover, using pifithrin-α, a pharmacological inhibitor of p53, it was demonstrated that the inhibitory effect of Nutlin-3a on IRinduced CXCL10 in J774A.1 macrophages is independent of p53. To the best of our knowledge, this study is the first to report the pathophysiological significance that the regulation of p38 MAPK phosphorylation by Nutlin-3a controls IR-induced CXCL10 production in J774A.1 macrophages.
Keywords : Ionizing radiation, Macrophage, CXCL10, Nutlin-3a, p38 MAPK, p53