{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:20Z","timestamp":1787028500412,"version":"build-2736575974"},"reference-count":68,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T00:00:00Z","timestamp":1675814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Korean government","award":["NRF-2018R1D1A3B07044209"],"award-info":[{"award-number":["NRF-2018R1D1A3B07044209"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Risk signals are characteristic of many common inflammatory diseases and can function to activate nucleotide-binding oligomerization (NLR) family pyrin domain-containing 3 (NLRP3), the innate immune signal receptor in cytoplasm. The NLRP3 inflammasome plays an important role in the development of liver fibrosis. Activated NLRP3 nucleates the assembly of inflammasomes, leading to the secretion of interleukin (IL)-1\u03b2 and IL-18, the activation of caspase-1, and the initiation of the inflammatory process. Therefore, it is essential to inhibit the activation of the NLRP3 inflammasome, which plays a vital role in the immune response and in initiating inflammation. RAW 264.7 and LX-2 cells were primed with lipopolysaccharide (LPS) for 4 h and subsequently stimulated for 30 min with 5 mM of adenosine 5\u2032-triphosphate (ATP) to activate the NLRP3 inflammasome. Thymosin beta 4 (T\u03b24) was supplemented to RAW264.7 and LX-2 cells 30 min before ATP was added. As a result, we investigated the effects of T\u03b24 on the NLRP3 inflammasome. T\u03b24 prevented LPS-induced NLRP3 priming by inhibiting NF-kB and JNK\/p38 MAPK expression and the LPS and ATP-induced production of reactive oxygen species. Moreover, T\u03b24 induced autophagy by controlling autophagy markers (LC3A\/B and p62) through the inhibition of the PI3K\/AKT\/mTOR pathway. LPS combined with ATP significantly increased thee protein expression of inflammatory mediators and NLRP3 inflammasome markers. These events were remarkably suppressed by T\u03b24. In conclusion, T\u03b24 attenuated NLRP3 inflammasomes by inhibiting NLRP3 inflammasome-related proteins (NLRP3, ASC, IL-1\u03b2, and caspase-1). Our results indicate that T\u03b24 attenuated the NLRP3 inflammasome through multiple signaling pathway regulations in macrophage and hepatic stellate cells. Therefore, based on the above findings, it is hypothesized that T\u03b24 could be a potential inflammatory therapeutic agent targeting the NLRP3 inflammasome in hepatic fibrosis regulation.<\/jats:p>","DOI":"10.3390\/ijms24043439","type":"journal-article","created":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T02:32:07Z","timestamp":1675909927000},"page":"3439","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Thymosin Beta 4 Inhibits LPS and ATP-Induced Hepatic Stellate Cells via the Regulation of Multiple Signaling Pathways"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2959-5610","authenticated-orcid":false,"given":"Jihye","family":"Choi","sequence":"first","affiliation":[{"name":"Department of Laboratory Animal Medicine, College of Veterinary Medicine, Jeonbuk National University, Iksan 54596, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunsang","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Medicine, College of Veterinary Medicine, Jeonbuk National University, Iksan 54596, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hwal","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Medicine, College of Veterinary Medicine, Jeonbuk National University, Iksan 54596, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangmin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Medicine, College of Veterinary Medicine, Jeonbuk National University, Iksan 54596, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeju","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Medicine, College of Veterinary Medicine, Jeonbuk National University, Iksan 54596, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeonghyeon","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Medicine, College of Veterinary Medicine, Jeonbuk National University, Iksan 54596, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jungkee","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Medicine, College of Veterinary Medicine, Jeonbuk National University, Iksan 54596, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1186\/s10020-020-00207-w","article-title":"Exosomal miR-223 derived from natural killer cells inhibits hepatic stellate cell activation by suppressing autophagy","volume":"26","author":"Wang","year":"2020","journal-title":"Mol. 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