{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T11:01:32Z","timestamp":1771930892620,"version":"3.50.1"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T00:00:00Z","timestamp":1645574400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Inflammatory disorder and acinar cell death contribute to the initiation and progression of severe acute pancreatitis (SAP). Adenosine kinase (ADK) has potential effects on both inflammation and cell death. However, the role of ADK in SAP remains to be explored.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> To establish an experimental SAP model, male C57BL\/6 mice were intraperitoneally injected with cerulein (50\u00a0\u03bcg\/kg, seven doses at hourly intervals) and LPS (10\u00a0mg\/kg, at the last cerulein injection). For ADK inhibition, ABT702 (1.5\u00a0mg\/kg) was intraperitoneally injected 1\u00a0h before cerulein treatment. The pancreas and serum were collected and analyzed to determine the severity of pancreatic injury and explore the potential pathophysiological mechanisms. Pancreatic acinar cells (AR42J) were used to explore the <jats:italic>in vitro<\/jats:italic> effects of ADK inhibition on cerulein\u2013induced inflammation and necroptotic cell death.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> ADK inhibition notably attenuated the severity of SAP, as indicated by the decreased serum amylase (7,416.76 \u00b1 1,457.76 vs. 4,581.89 \u00b1 1,175.04\u00a0U\/L) and lipase (46.51 \u00b1 11.50 vs. 32.94 \u00b1 11.46\u00a0U\/L) levels and fewer pancreatic histopathological alterations (histological scores: 6.433 \u00b1 0.60 vs. 3.77 \u00b1 0.70). MOMA-2 and CD11b staining confirmed that ADK inhibition prevented the infiltration of neutrophils and macrophages. The phosphorylation of nuclear factor-\u03baB (NF-\u03baB) was also reduced by ADK inhibition. ADK inhibition markedly limited the necrotic area of the pancreas and prevented the activation of the necroptotic signaling pathway. Endoplasmic reticulum (ER) stress was activated in the pancreas using the SAP model and cerulein\u2013treated AR42J cells whereas ADK inhibition reversed the activation of ER stress both <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>. Moreover, the alleviating effects of ADK inhibition on ER stress, inflammation, and cell necroptosis were eliminated by the adenosine A<jats:sub>2A<\/jats:sub> receptor antagonist.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> ADK inhibition reduced inflammation and necroptotic acinar cell death in SAP <jats:italic>via<\/jats:italic> the adenosine A<jats:sub>2A<\/jats:sub> receptor\/ER stress pathway, suggesting that ADK might be a potential therapeutic target for SAP.<\/jats:p>","DOI":"10.3389\/fcell.2022.827714","type":"journal-article","created":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T12:59:59Z","timestamp":1645621199000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Adenosine Kinase Inhibition Prevents Severe Acute Pancreatitis via Suppressing Inflammation and Acinar Cell Necroptosis"],"prefix":"10.3389","volume":"10","author":[{"given":"Shukun","family":"Sun","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuanxin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bailu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shengchuan","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiuhuan","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shujian","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuguo","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.jneuroim.2014.10.006","article-title":"Inhibition of Adenosine Kinase Attenuates Inflammation and Neurotoxicity in Traumatic Optic Neuropathy","volume":"277","author":"Ahmad","year":"2014","journal-title":"J. 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