PMID- 37851686 OWN - NLM STAT- MEDLINE DCOM- 20231023 LR - 20240216 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 18 IP - 10 DP - 2023 TI - Anti-inflammatory effects of cold atmospheric plasma irradiation on the THP-1 human acute monocytic leukemia cell line. PG - e0292267 LID - 10.1371/journal.pone.0292267 [doi] LID - e0292267 AB - Cold atmospheric plasma (CAP) has been studied and clinically applied to treat chronic wounds, cancer, periodontitis, and other diseases. CAP exerts cytotoxic, bactericidal, cell-proliferative, and anti-inflammatory effects on living tissues by generating reactive species. Therefore, CAP holds promise as a treatment for diseases involving chronic inflammation and bacterial infections. However, the cellular mechanisms underlying these anti-inflammatory effects of CAP are still unclear. Thus, this study aimed to elucidate the anti-inflammatory mechanisms of CAP in vitro. The human acute monocytic leukemia cell line, THP-1, was stimulated with lipopolysaccharide and irradiated with CAP, and the cytotoxic effects of CAP were evaluated. Time-course differentiation of gene expression was analyzed, and key transcription factors were identified via transcriptome analysis. Additionally, the nuclear localization of the CAP-induced transcription factor was examined using western blotting. The results indicated that CAP showed no cytotoxic effects after less than 70 s of irradiation and significantly inhibited interleukin 6 (IL6) expression after more than 40 s of irradiation. Transcriptome analysis revealed many differentially expressed genes (DEGs) following CAP irradiation at all time points. Cluster analysis classified the DEGs into four distinct groups, each with time-dependent characteristics. Gene ontology and gene set enrichment analyses revealed CAP-induced suppression of IL6 production, other inflammatory responses, and the expression of genes related to major histocompatibility complex (MHC) class II. Transcription factor analysis suggested that nuclear factor erythroid 2-related factor 2 (NRF2), which suppresses intracellular oxidative stress, is the most activated transcription factor. Contrarily, regulatory factor X5, which regulates MHC class II expression, is the most suppressed transcription factor. Western blotting revealed the nuclear localization of NRF2 following CAP irradiation. These data suggest that CAP suppresses the inflammatory response, possibly by promoting NRF2 nuclear translocation. CI - Copyright: (c) 2023 Hirasawa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. FAU - Hirasawa, Ito AU - Hirasawa I AD - Department of Periodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan. AD - Sekisui Chemical Co., Ltd., Ibaraki, Japan. FAU - Odagiri, Haruka AU - Odagiri H AD - Sekisui Chemical Co., Ltd., Ibaraki, Japan. FAU - Park, Giri AU - Park G AD - Sekisui Chemical Co., Ltd., Ibaraki, Japan. FAU - Sanghavi, Rutvi AU - Sanghavi R AD - Sekisui Chemical Co., Ltd., Ibaraki, Japan. FAU - Oshita, Takaya AU - Oshita T AD - Sekisui Chemical Co., Ltd., Ibaraki, Japan. FAU - Togi, Akiko AU - Togi A AD - Sekisui Chemical Co., Ltd., Ibaraki, Japan. FAU - Yoshikawa, Katsunori AU - Yoshikawa K AD - Sekisui Chemical Co., Ltd., Ibaraki, Japan. FAU - Mizutani, Koji AU - Mizutani K AUID- ORCID: 0000-0002-1610-7430 AD - Department of Periodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan. FAU - Takeuchi, Yasuo AU - Takeuchi Y AUID- ORCID: 0000-0003-4193-219X AD - Department of Lifetime Oral Health Care Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan. FAU - Kobayashi, Hiroaki AU - Kobayashi H AD - Department of Periodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan. FAU - Katagiri, Sayaka AU - Katagiri S AD - Department of Periodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan. FAU - Iwata, Takanori AU - Iwata T AD - Department of Periodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan. FAU - Aoki, Akira AU - Aoki A AUID- ORCID: 0000-0001-5936-1116 AD - Department of Periodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20231018 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (NF-E2-Related Factor 2) RN - 0 (Plasma Gases) RN - 0 (Interleukin-6) RN - 0 (Anti-Inflammatory Agents) RN - 0 (Lipopolysaccharides) SB - IM EIN - PLoS One. 2024 Feb 16;19(2):e0299329. PMID: 38363793 MH - Humans MH - NF-E2-Related Factor 2/genetics/metabolism MH - THP-1 Cells MH - *Leukemia, Monocytic, Acute MH - *Plasma Gases/pharmacology MH - Interleukin-6 MH - Anti-Inflammatory Agents/pharmacology MH - Cell Line MH - Lipopolysaccharides PMC - PMC10584116 COIS- The authors have declared that no competing interests exist. EDAT- 2023/10/18 18:43 MHDA- 2023/10/23 01:18 PMCR- 2023/10/18 CRDT- 2023/10/18 13:44 PHST- 2023/06/21 00:00 [received] PHST- 2023/09/15 00:00 [accepted] PHST- 2023/10/23 01:18 [medline] PHST- 2023/10/18 18:43 [pubmed] PHST- 2023/10/18 13:44 [entrez] PHST- 2023/10/18 00:00 [pmc-release] AID - PONE-D-23-17572 [pii] AID - 10.1371/journal.pone.0292267 [doi] PST - epublish SO - PLoS One. 2023 Oct 18;18(10):e0292267. doi: 10.1371/journal.pone.0292267. eCollection 2023.