PMID- 37622701 OWN - NLM STAT- Publisher LR - 20230825 IS - 1873-4316 (Electronic) IS - 1389-2010 (Linking) DP - 2023 Aug 24 TI - 5-Methylthiopentyl Isothiocyanate, a Sulforaphane Analogue, Inhibits Pro-inflammatory Cytokines by Regulating LPS/ATP-mediated NLRP3 Inflammasome Activation. LID - 10.2174/1389201024666230824093927 [doi] AB - BACKGROUND: Pro-inflammatory cytokines secreted from activated macrophages and astrocytes are crucial mediators of inflammation for host defense. Among them, the secretion of IL-1beta, a major pro-inflammatory cytokine, is especially mediated by the activation of NLRP3 inflammasome. Pro-IL-1beta, which is produced in response to the invaded pathogens, such as LPS, is cleaved and matured in the NLRP3 inflammasome by the recognition of ATP. Excessively activated IL-1beta induces other immune cells, resulting in the up-regulation of inflammation. Therefore, regulation of NLRP3 inflammasome can be a good strategy for alleviating inflammation. OBJECTIVE: Our study aimed to examine whether 5-methylthiopentyl isothiocyanate, a sulforaphane analogue (berteroin), has an anti-inflammatory effect on the NLRP3 inflammasome activation induced by LPS and ATP. METHODS: Primary bone marrow-derived macrophages (BMDMs) and astrocytes were stimulated by LPS and ATP with the treatment of 5-methylthiopentyl isothiocyanate, a sulforaphane analogue. The secretion of pro-inflammatory cytokines was measured by ELISA, and the expression level of NLRP3 inflammasome-associated proteins was detected by western blot. The association of NLRP3 inflammasome was assessed by co-immunoprecipitation, and the formation of ASC specks was evaluated by fluorescent microscope. RESULTS: 5-Methylthiopentyl isothiocyanate, a sulforaphane analogue (berteroin), decreased the release of pro-inflammatory cytokines, IL-1beta, and IL-6 in the BMDMs. Berteroin notably prevented the formation of both NLRP3 inflammasome and ASC specks, which reduced the secretion of IL-1beta. Additionally, berteroin reduced the IL-1beta secretion and cleaved IL-1beta expression in the primary astrocytes. DISCUSSION AND CONCLUSION: These results indicated the anti-inflammatory effects of 5-methylthiopentyl isothiocyanate (berteroin) by regulating NLRP3 inflammasome activation, suggesting that berteroin could be the potential natural drug candidate for the regulation of inflammation. CI - Copyright(c) Bentham Science Publishers; For any queries, please email at epub@benthamscience.net. FAU - Choi, Su-Bin AU - Choi SB AD - Department of Biomedical Engineering, College of Life Science and Biotechnology, Dongguk University, Seoul 04620, Republic of Korea. FAU - Kim, Ji-Hye AU - Kim JH AD - Department of Biomedical Engineering, College of Life Science and Biotechnology, Dongguk University, Seoul 04620, Republic of Korea. FAU - Kwon, Sehee AU - Kwon S AD - Department of Biomedical Engineering, College of Life Science and Biotechnology, Dongguk University, Seoul 04620, Republic of Korea. FAU - Ahn, Na-Hyun AU - Ahn NH AD - Department of Biomedical Engineering, College of Life Science and Biotechnology, Dongguk University, Seoul 04620, Republic of Korea. FAU - Lee, Joo-Hee AU - Lee JH AD - Department of Biomedical Engineering, College of Life Science and Biotechnology, Dongguk University, Seoul 04620, Republic of Korea. FAU - Yang, Woong-Suk AU - Yang WS AD - National Institute for Nanomaterials Technology (NINT), POSTECH, 77, Pohang 37673, Republic of Korea. FAU - Kim, Cheorl-Ho AU - Kim CH AD - Department of Biological Sciences, Sungkyunkwan University and Samsung Advanced Institute of Health Science and Technology, Suwon 1649, Republic of Korea. FAU - Yang, Seung-Hoon AU - Yang SH AUID- ORCID: 0000-0002-6880-8861 AD - Department of Biomedical Engineering, College of Life Science and Biotechnology, Dongguk University, Seoul 04620, Republic of Korea. LA - eng PT - Journal Article DEP - 20230824 PL - Netherlands TA - Curr Pharm Biotechnol JT - Current pharmaceutical biotechnology JID - 100960530 SB - IM OTO - NOTNLM OT - 5-Methylthiopentyl isothiocyanate OT - ASC spec OT - NLRP3 inflammasome OT - astrocyte OT - primary bone marrow-derived macropahges (BMDMs) OT - pro-inflammatory cytokine OT - sulforaphane analogue (berteroin) EDAT- 2023/08/25 12:43 MHDA- 2023/08/25 12:43 CRDT- 2023/08/25 08:13 PHST- 2023/01/06 00:00 [received] PHST- 2023/04/25 00:00 [revised] PHST- 2023/05/26 00:00 [accepted] PHST- 2023/08/25 12:43 [medline] PHST- 2023/08/25 12:43 [pubmed] PHST- 2023/08/25 08:13 [entrez] AID - CPB-EPUB-134007 [pii] AID - 10.2174/1389201024666230824093927 [doi] PST - aheadofprint SO - Curr Pharm Biotechnol. 2023 Aug 24. doi: 10.2174/1389201024666230824093927.