{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:29:18Z","timestamp":1790659758215,"version":"4.1.0"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170660"],"award-info":[{"award-number":["82170660"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018542","name":"Natural Science Foundation of Sichuan Province","doi-asserted-by":"publisher","award":["2022NSFSC0825"],"award-info":[{"award-number":["2022NSFSC0825"]}],"id":[{"id":"10.13039\/501100018542","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Inflamm. Res."],"published-print":{"date-parts":[[2023,9]]},"DOI":"10.1007\/s00011-023-01794-0","type":"journal-article","created":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T12:02:05Z","timestamp":1695124925000},"page":"1919-1932","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Nafamostat mesilate prevented caerulein-induced pancreatic injury by targeting HDAC6-mediated NLRP3 inflammasome activation"],"prefix":"10.1007","volume":"72","author":[{"given":"Peng","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Jun","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Qi","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Rui","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Dong","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,9,19]]},"reference":[{"key":"1794_CR1","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1007\/BF01657981","volume":"5","author":"V Becker","year":"1981","unstructured":"Becker V. Pathological anatomy and pathogenesis of acute pancreatitis. World J Surg. 1981;5:303\u201313.","journal-title":"World J Surg"},{"key":"1794_CR2","doi-asserted-by":"publisher","first-page":"1328","DOI":"10.1111\/jgh.12584","volume":"29","author":"R Liu","year":"2014","unstructured":"Liu R, Qi H, Wang J, Wang Y, Cui L, Wen Y, et al. Ulinastatin activates the renin-angiotensin system to ameliorate the pathophysiology of severe acute pancreatitis. J Gastroenterol Hepatol. 2014;29:1328\u201337.","journal-title":"J Gastroenterol Hepatol"},{"key":"1794_CR3","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.3109\/00365528608996413","volume":"21","author":"TE Ruud","year":"1986","unstructured":"Ruud TE, Aasen AO, Stadaas JO, Aune S. Effects on peritoneal proteolysis and hemodynamics of prophylactic and therapeutic infusions of high doses of aprotinin in experimental acute pancreatitis. Scand J Gastroenterol. 1986;21:1011\u20137.","journal-title":"Scand J Gastroenterol"},{"key":"1794_CR4","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1007\/BF02938474","volume":"4","author":"JR Wisner Jr","year":"1989","unstructured":"Wisner JR Jr, Ozawa S, Renner IG. The effects of nafamostat mesilate (FUT-175) on caerulein-induced acute pancreatitis in the rat. Int J Pancreatol. 1989;4:383\u201390.","journal-title":"Int J Pancreatol"},{"key":"1794_CR5","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1097\/00006676-198703000-00010","volume":"2","author":"JR Wisner Jr","year":"1987","unstructured":"Wisner JR Jr, Renner IG, Grendell JH, Niederau C, Ferrell LD. Gabexate mesilate (FOY) protects against ceruletide-induced acute pancreatitis in the rat. Pancreas. 1987;2:181\u20136.","journal-title":"Pancreas"},{"key":"1794_CR6","first-page":"488","volume":"8","author":"CC Chen","year":"2007","unstructured":"Chen CC, Wang SS, Lee FY. Action of antiproteases on the inflammatory response in acute pancreatitis. JOP. 2007;8:488\u201394.","journal-title":"JOP"},{"key":"1794_CR7","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1055\/s-0038-1650224","volume":"75","author":"S Sundaram","year":"1996","unstructured":"Sundaram S, Gikakis N, Hack CE, Niewiarowski S, Edmunds LH Jr, Koneti Rao A, et al. Nafamostat mesilate, a broad spectrum protease inhibitor, modulates platelet, neutrophil and contact activation in simulated extracorporeal circulation. Thromb Haemost. 1996;75:76\u201382.","journal-title":"Thromb Haemost"},{"key":"1794_CR8","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1111\/cns.12801","volume":"24","author":"HQ Duan","year":"2018","unstructured":"Duan HQ, Wu QL, Yao X, Fan BY, Shi HY, Zhao CX, et al. Nafamostat mesilate attenuates inflammation and apoptosis and promotes locomotor recovery after spinal cord injury. CNS Neurosci Ther. 2018;24:429\u201338.","journal-title":"CNS Neurosci Ther"},{"key":"1794_CR9","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/s12974-021-02357-y","volume":"19","author":"AG Yates","year":"2022","unstructured":"Yates AG, Weglinski CM, Ying Y, Dunstan IK, Strekalova T, Anthony DC. Nafamostat reduces systemic inflammation in TLR7-mediated virus-like illness. J Neuroinflammation. 2022;19:8.","journal-title":"J Neuroinflammation"},{"key":"1794_CR10","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1053\/j.gastro.2011.03.041","volume":"141","author":"R Hoque","year":"2011","unstructured":"Hoque R, Sohail M, Malik A, Sarwar S, Luo Y, Shah A, et al. TLR9 and the NLRP3 inflammasome link acinar cell death with inflammation in acute pancreatitis. Gastroenterology. 2011;141:358\u201369.","journal-title":"Gastroenterology"},{"key":"1794_CR11","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1038\/nrd.2018.97","volume":"17","author":"MSJ Mangan","year":"2018","unstructured":"Mangan MSJ, Olhava EJ, Roush WR, Seidel HM, Glick GD, Latz E. Targeting the NLRP3 inflammasome in inflammatory diseases. Nat Rev Drug Discov. 2018;17:588\u2013606.","journal-title":"Nat Rev Drug Discov"},{"key":"1794_CR12","doi-asserted-by":"publisher","first-page":"5658","DOI":"10.1039\/D1FO01154E","volume":"12","author":"ZL Luo","year":"2021","unstructured":"Luo ZL, Sun HY, Wu XB, Cheng L, Ren JD. Epigallocatechin-3-gallate attenuates acute pancreatitis induced lung injury by targeting mitochondrial reactive oxygen species triggered NLRP3 inflammasome activation. Food Funct. 2021;12:5658\u201367.","journal-title":"Food Funct"},{"key":"1794_CR13","doi-asserted-by":"publisher","first-page":"4446","DOI":"10.1111\/bph.14806","volume":"176","author":"X Pan","year":"2019","unstructured":"Pan X, Fang X, Wang F, Li H, Niu W, Liang W, et al. Butyrate ameliorates caerulein-induced acute pancreatitis and associated intestinal injury by tissue-specific mechanisms. Br J Pharmacol. 2019;176:4446\u201361.","journal-title":"Br J Pharmacol"},{"key":"1794_CR14","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/930894","volume":"2014","author":"JD Ren","year":"2014","unstructured":"Ren JD, Ma J, Hou J, Xiao WJ, Jin WH, Wu J, et al. Hydrogen-rich saline inhibits NLRP3 inflammasome activation and attenuates experimental acute pancreatitis in mice. Mediators Inflamm. 2014;2014: 930894.","journal-title":"Mediators Inflamm"},{"key":"1794_CR15","first-page":"4310","volume":"14","author":"L Wang","year":"2022","unstructured":"Wang L, Wang N, Shi G, Sun S. Follistatin-like 1 ameliorates severe acute pancreatitis associated lung injury via inhibiting the activation of NLRP3 inflammasome and NF-kappaB pathway. Am J Transl Res. 2022;14:4310\u201320.","journal-title":"Am J Transl Res"},{"key":"1794_CR16","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1016\/j.bbi.2016.03.019","volume":"56","author":"C Li","year":"2016","unstructured":"Li C, Wang J, Fang Y, Liu Y, Chen T, Sun H, et al. Nafamostat mesilate improves function recovery after stroke by inhibiting neuroinflammation in rats. Brain Behav Immun. 2016;56:230\u201345.","journal-title":"Brain Behav Immun"},{"key":"1794_CR17","doi-asserted-by":"publisher","first-page":"924","DOI":"10.21037\/atm-21-1882","volume":"9","author":"Y Lin","year":"2021","unstructured":"Lin Y, Xu D, Gao F, Zheng X. Ulinastatin inhibits NLRP3-induced apoptosis in a PD cell model. Ann Transl Med. 2021;9:924.","journal-title":"Ann Transl Med"},{"key":"1794_CR18","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1002\/ddr.22010","volume":"84","author":"Z Liu","year":"2023","unstructured":"Liu Z, Zhu X, Xu C, Min F, Yu G, Chen C. Ulinastatin ameliorates the malignant progression of prostate cancer cells by blocking the RhoA\/ROCK\/NLRP3 pathway. Drug Dev Res. 2023;84:36\u201344.","journal-title":"Drug Dev Res"},{"key":"1794_CR19","doi-asserted-by":"crossref","unstructured":"Qiu J, Xiao X, Gao X, Zhang Y. Ulinastatin protects against sepsis\u2011induced myocardial injury by inhibiting NLRP3 inflammasome activation. Mol Med Rep 2021; 24.","DOI":"10.3892\/mmr.2021.12369"},{"key":"1794_CR20","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1097\/00000658-199201000-00007","volume":"215","author":"J Schmidt","year":"1992","unstructured":"Schmidt J, Rattner DW, Lewandrowski K, Compton CC, Mandavilli U, Knoefel WT, et al. A better model of acute pancreatitis for evaluating therapy. Ann Surg. 1992;215:44\u201356.","journal-title":"Ann Surg"},{"key":"1794_CR21","doi-asserted-by":"publisher","first-page":"787","DOI":"10.4049\/jimmunol.0901363","volume":"183","author":"FG Bauernfeind","year":"2009","unstructured":"Bauernfeind FG, Horvath G, Stutz A, Alnemri ES, MacDonald K, Speert D, et al. Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. J Immunol. 2009;183:787\u201391.","journal-title":"J Immunol"},{"key":"1794_CR22","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1016\/S1567-5769(03)00146-2","volume":"3","author":"S Noguchi","year":"2003","unstructured":"Noguchi S, Nakatsuka M, Konishi H, Kamada Y, Chekir C, Kudo T. Nafamostat mesilate suppresses NF-kappaB activation and NO overproduction in LPS-treated macrophages. Int Immunopharmacol. 2003;3:1335\u201344.","journal-title":"Int Immunopharmacol"},{"key":"1794_CR23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.atherosclerosis.2020.11.021","volume":"317","author":"S Xu","year":"2021","unstructured":"Xu S, Chen H, Ni H, Dai Q. Targeting HDAC6 attenuates nicotine-induced macrophage pyroptosis via NF-kappaB\/NLRP3 pathway. Atherosclerosis. 2021;317:1\u20139.","journal-title":"Atherosclerosis"},{"key":"1794_CR24","doi-asserted-by":"publisher","first-page":"169","DOI":"10.4149\/gpb_2019058","volume":"39","author":"Q Yang","year":"2020","unstructured":"Yang Q, Li S, Zhou Z, Fu M, Yang X, Hao K, et al. HDAC6 inhibitor Cay10603 inhibits high glucose-induced oxidative stress, inflammation and apoptosis in retinal pigment epithelial cells via regulating NF-kappaB and NLRP3 inflammasome pathway. Gen Physiol Biophys. 2020;39:169\u201377.","journal-title":"Gen Physiol Biophys"},{"key":"1794_CR25","doi-asserted-by":"crossref","unstructured":"Magupalli VG, Negro R, Tian Y, Hauenstein AV, Di Caprio G, Skillern W, et al. HDAC6 mediates an aggresome-like mechanism for NLRP3 and pyrin inflammasome activation. Science 2020; 369.","DOI":"10.1126\/science.aas8995"},{"key":"1794_CR26","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1177\/1087057116629381","volume":"21","author":"CW Hsu","year":"2016","unstructured":"Hsu CW, Shou D, Huang R, Khuc T, Dai S, Zheng W, et al. Identification of HDAC Inhibitors Using a Cell-Based HDAC I\/II Assay. J Biomol Screen. 2016;21:643\u201352.","journal-title":"J Biomol Screen"},{"key":"1794_CR27","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.763831","volume":"12","author":"P Chang","year":"2021","unstructured":"Chang P, Li H, Hu H, Li Y, Wang T. The Role of HDAC6 in Autophagy and NLRP3 Inflammasome. Front Immunol. 2021;12: 763831.","journal-title":"Front Immunol"},{"key":"1794_CR28","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006799","volume":"13","author":"O Moreno-Gonzalo","year":"2017","unstructured":"Moreno-Gonzalo O, Ramirez-Huesca M, Blas-Rus N, Cibrian D, Saiz ML, Jorge I, et al. HDAC6 controls innate immune and autophagy responses to TLR-mediated signalling by the intracellular bacteria Listeria monocytogenes. PLoS Pathog. 2017;13: e1006799.","journal-title":"PLoS Pathog"},{"key":"1794_CR29","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.taap.2019.03.017","volume":"370","author":"L Liu","year":"2019","unstructured":"Liu L, Zhou X, Shetty S, Hou G, Wang Q, Fu J. HDAC6 inhibition blocks inflammatory signaling and caspase-1 activation in LPS-induced acute lung injury. Toxicol Appl Pharmacol. 2019;370:178\u201383.","journal-title":"Toxicol Appl Pharmacol"},{"key":"1794_CR30","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.freeradbiomed.2016.05.014","volume":"97","author":"GS Youn","year":"2016","unstructured":"Youn GS, Lee KW, Choi SY, Park J. Overexpression of HDAC6 induces pro-inflammatory responses by regulating ROS-MAPK-NF-kappaB\/AP-1 signaling pathways in macrophages. Free Radic Biol Med. 2016;97:14\u201323.","journal-title":"Free Radic Biol Med"},{"key":"1794_CR31","doi-asserted-by":"publisher","first-page":"7218","DOI":"10.1111\/jcmm.16751","volume":"25","author":"Q Chen","year":"2021","unstructured":"Chen Q, Wang Y, Jiao F, Cao P, Shi C, Pei M, et al. HDAC6 inhibitor ACY1215 inhibits the activation of NLRP3 inflammasome in acute liver failure by regulating the ATM\/F-actin signalling pathway. J Cell Mol Med. 2021;25:7218\u201328.","journal-title":"J Cell Mol Med"},{"key":"1794_CR32","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.2147\/JIR.S302391","volume":"14","author":"Y Wang","year":"2021","unstructured":"Wang Y, Li X, Chen Q, Jiao F, Shi C, Pei M, et al. Histone Deacetylase 6 Regulates the Activation of M1 Macrophages by the Glycolytic Pathway During Acute Liver Failure. J Inflamm Res. 2021;14:1473\u201385.","journal-title":"J Inflamm Res"},{"key":"1794_CR33","doi-asserted-by":"publisher","first-page":"78","DOI":"10.3389\/fnagi.2020.00078","volume":"12","author":"S Yan","year":"2020","unstructured":"Yan S, Wei X, Jian W, Qin Y, Liu J, Zhu S, et al. Pharmacological Inhibition of HDAC6 Attenuates NLRP3 Inflammatory Response and Protects Dopaminergic Neurons in Experimental Models of Parkinson\u2019s Disease. Front Aging Neurosci. 2020;12:78.","journal-title":"Front Aging Neurosci"},{"key":"1794_CR34","doi-asserted-by":"publisher","first-page":"6720","DOI":"10.1038\/s41598-018-25123-2","volume":"8","author":"N Piippo","year":"2018","unstructured":"Piippo N, Korhonen E, Hytti M, Skottman H, Kinnunen K, Josifovska N, et al. Hsp90 inhibition as a means to inhibit activation of the NLRP3 inflammasome. Sci Rep. 2018;8:6720.","journal-title":"Sci Rep"},{"key":"1794_CR35","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1016\/j.molcel.2005.04.021","volume":"18","author":"JJ Kovacs","year":"2005","unstructured":"Kovacs JJ, Murphy PJ, Gaillard S, Zhao X, Wu JT, Nicchitta CV, et al. HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor. Mol Cell. 2005;18:601\u20137.","journal-title":"Mol Cell"},{"key":"1794_CR36","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1016\/j.tcb.2005.09.003","volume":"15","author":"S Aoyagi","year":"2005","unstructured":"Aoyagi S, Archer TK. Modulating molecular chaperone Hsp90 functions through reversible acetylation. Trends Cell Biol. 2005;15:565\u20137.","journal-title":"Trends Cell Biol"},{"key":"1794_CR37","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.938391","volume":"13","author":"Q Hou","year":"2022","unstructured":"Hou Q, Kan S, Wang Z, Shi J, Zeng C, Yang D, et al. Inhibition of HDAC6 With CAY10603 Ameliorates Diabetic Kidney Disease by Suppressing NLRP3 Inflammasome. Front Pharmacol. 2022;13: 938391.","journal-title":"Front Pharmacol"},{"key":"1794_CR38","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.121.024205","volume":"11","author":"J Xu","year":"2022","unstructured":"Xu J, Zhao X, Jiang X, He L, Wu X, Wang J, et al. Tubastatin A Improves Post-Resuscitation Myocardial Dysfunction by Inhibiting NLRP3-Mediated Pyroptosis Through Enhancing Transcription Factor EB Signaling. J Am Heart Assoc. 2022;11: e024205.","journal-title":"J Am Heart Assoc"}],"container-title":["Inflammation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00011-023-01794-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00011-023-01794-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00011-023-01794-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T05:04:59Z","timestamp":1695877499000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00011-023-01794-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9]]},"references-count":38,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2023,9]]}},"alternative-id":["1794"],"URL":"https:\/\/doi.org\/10.1007\/s00011-023-01794-0","relation":{},"ISSN":["1023-3830","1420-908X"],"issn-type":[{"value":"1023-3830","type":"print"},{"value":"1420-908X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9]]},"assertion":[{"value":"8 June 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 August 2023","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 September 2023","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 September 2023","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that there are no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The animal care and experimental protocols were approved by IACUC of the University of Electronic Science and Technology of China, in accordance with NIH guidelines for the Care and Use of Laboratory Animals.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}}]}}