دورية أكاديمية
Deletion of myeloid-specific Orai1 calcium channel does not affect pancreatic tissue damage in experimental acute pancreatitis.
| العنوان: | Deletion of myeloid-specific Orai1 calcium channel does not affect pancreatic tissue damage in experimental acute pancreatitis. |
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| المؤلفون: | Mei W; Department of General Surgery, Xuanwu Hospital Capital Medical University, Beijing 100053, China., Zhang X; Center for Biomarker Discovery and Validation, National Infrastructures for Translational Medicine (PUMCH), Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, 100730, China; State Key Laboratory of Complex, Severe, and Rare Diseases, Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100730, China; Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, 100730, China., Niu M; Department of Gastroenterology and Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201600, China., Li L; Department of Gastroenterology and Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201600, China., Guo X; Center for Biomarker Discovery and Validation, National Infrastructures for Translational Medicine (PUMCH), Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, 100730, China; State Key Laboratory of Complex, Severe, and Rare Diseases, Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100730, China; Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, 100730, China; Department of Gastroenterology and Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201600, China; Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China., Wang G; Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China., Pandol S; Department of Medicine, Cedars-Sinai Medical Center, Los Angel, CA, 90048, USA., Wen L; Center for Biomarker Discovery and Validation, National Infrastructures for Translational Medicine (PUMCH), Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, 100730, China; State Key Laboratory of Complex, Severe, and Rare Diseases, Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100730, China. Electronic address: wenli7007@gmail.com., Cao F; Department of General Surgery, Xuanwu Hospital Capital Medical University, Beijing 100053, China. Electronic address: f.cao@xwhosp.org. |
| المصدر: | Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] [Pancreatology] 2024 Jun; Vol. 24 (4), pp. 528-537. Date of Electronic Publication: 2024 Apr 05. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Country of Publication: Switzerland NLM ID: 100966936 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1424-3911 (Electronic) Linking ISSN: 14243903 NLM ISO Abbreviation: Pancreatology Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2012- : New Delhi : Elsevier India Original Publication: Basel ; New York : Karger, c2001- |
| مواضيع طبية MeSH: | ORAI1 Protein*/metabolism , ORAI1 Protein*/genetics , Pancreatitis*/pathology , Pancreatitis*/metabolism , Pancreatitis*/chemically induced , Pancreatitis*/genetics , Macrophages*/metabolism , Pancreas*/pathology , Pancreas*/metabolism, Animals ; Mice ; Mice, Inbred C57BL ; Myeloid Cells/metabolism ; Mice, Knockout ; Disease Models, Animal ; Gene Deletion |
| مستخلص: | Background: Store-operated Ca 2+ entry (SOCE) mediated by ORAI1 channel plays a crucial role in acute pancreatitis (AP). Macrophage is an important regulator in amplifying pancreatic tissue damage, but little is known about the role of ORAI1 in macrophages. In this study, we examined the effects of macrophage-specific ORAI1 on pancreatic tissue damage in AP. Method: Myeloid-specific Orai1 deficient mice was generated by crossing a LysM-Cre mouse line with Orai1 f/f mice. Bone marrow-derived macrophages (BMDMs) were isolated, cultured, and stimulated to induce M1 or M2 macrophage polarization. Intracellular Ca 2+ signals were measured by time-lapse confocal microscope imaging, with a Ca 2+ indicator (Fluo 4). Experimental AP was induced by hourly intraperitoneal injections of caerulein or retrograde biliopancreatic infusion of sodium taurocholate. Pancreatic tissue damage was assessed by histopathological scoring and immunostaining. Sepsis was induced by intraperitoneal injection of lipopolysaccharide; organ damage and serum pro-inflammatory cytokines were measured. Result: Myeloid-specific Orai1 deletion exhibited minimal effect on SOCE in M0 macrophages and promoted M2 macrophage polarization ex vivo. Myeloid-specific Orai1 deletion did not affect pancreatic tissue damage, nor neutrophil or macrophage infiltration in two models of AP. Similarly, myeloid-specific Orai1 deletion did not influence overall survival rate in a model of sepsis, nor lung, kidney, and liver damage; while serum pro-inflammatory cytokines, including IL-6, TNF-α, and IL-1β were higher in Orai1 ΔLysM mice, but were largely reduced in mice with Orai1 inhibitor. Conclusion: Our data suggest that ORAI1 may not be a predominant SOCE channel in macrophages and play a limited role in mediating pancreatic tissue damage in AP. Competing Interests: Declaration of competing interest All the authors have no conflict of interest. (Copyright © 2024 IAP and EPC. Published by Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Acute pancreatitis; Macrophages; Orai1; Tissue damages; sepsis |
| المشرفين على المادة: | 0 (ORAI1 Protein) 0 (Orai1 protein, mouse) |
| تواريخ الأحداث: | Date Created: 20240418 Date Completed: 20240610 Latest Revision: 20240620 |
| رمز التحديث: | 20240620 |
| DOI: | 10.1016/j.pan.2024.04.001 |
| PMID: | 38637233 |
| قاعدة البيانات: | MEDLINE |
Full Text via ClinicalKey 
Full Text Finder | تدمد: | 1424-3911 |
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| DOI: | 10.1016/j.pan.2024.04.001 |