Yi-shan Zheng1, Zong-sheng Wu, Lu-yao Zhang, Lu Ke, Wei-qin Li, Ning Li, Jie-shou Li. 1. From the *Department of General Surgery, Jinling Hospital, School of Medicine, Nanjing University; and †Intensive Care Unit, Second Affiliated Hospital of Southeast University, Nanjing, Jiangsu, China.
Abstract
OBJECTIVES: Activation of "nicotinic anti-inflammatory pathway" could reduce severity of inflammation and injury induced by acute pancreatitis. However, the role of regulatory T (Treg) cells in this pathway is unclear. METHODS: Severe acute pancreatitis (SAP) was induced in mice through retrograde injection of 50-μL 2% Na-taurocholate into the pancreatic duct of the mouse. In nicotine treatment group, nicotine (50, 100, and 300 μg/kg) was administered 1 hour before and after SAP operation through intraperitoneal injection. We compared the properties of Treg cell percentage and specific marker such as cytotoxic T-lymphocyte antigen 4 and forkhead box transcription factor forkhead/winged helix transcription factor p3 on Treg using quantitative reverse transcription polymerase chain reaction and flow cytometry. All experiment animal serum cytokines were measured using enzyme-linked immunosorbent assay. One-way analysis of variance was applied to evaluate the experimental data and for statistical comparisons. The survival rate data were analyzed using the log-rank test. RESULTS: Nicotine significantly protected mice from lethal SAP in a dose-dependent fashion by inhibiting tissue injury, digestive enzyme production, and proinflammatory cytokines production. Moreover, nicotine up-regulated the number and suppressive capacity of CD4 CD25 Treg via inducing the expression of immunoregulatory molecules and transforming growth factor β1 elevation. CONCLUSIONS: Modulating immunoregulation of CD4 CD25 Treg is a critical mechanism for nicotinic anti-inflammatory pathway and it may be feasible to use selective agonists as an immunotherapy for SAP.
OBJECTIVES: Activation of "nicotinic anti-inflammatory pathway" could reduce severity of inflammation and injury induced by acute pancreatitis. However, the role of regulatory T (Treg) cells in this pathway is unclear. METHODS: Severe acute pancreatitis (SAP) was induced in mice through retrograde injection of 50-μL 2% Na-taurocholate into the pancreatic duct of the mouse. In nicotine treatment group, nicotine (50, 100, and 300 μg/kg) was administered 1 hour before and after SAP operation through intraperitoneal injection. We compared the properties of Treg cell percentage and specific marker such as cytotoxic T-lymphocyte antigen 4 and forkhead box transcription factor forkhead/winged helix transcription factor p3 on Treg using quantitative reverse transcription polymerase chain reaction and flow cytometry. All experiment animal serum cytokines were measured using enzyme-linked immunosorbent assay. One-way analysis of variance was applied to evaluate the experimental data and for statistical comparisons. The survival rate data were analyzed using the log-rank test. RESULTS:Nicotine significantly protected mice from lethal SAP in a dose-dependent fashion by inhibiting tissue injury, digestive enzyme production, and proinflammatory cytokines production. Moreover, nicotine up-regulated the number and suppressive capacity of CD4CD25 Treg via inducing the expression of immunoregulatory molecules and transforming growth factor β1 elevation. CONCLUSIONS: Modulating immunoregulation of CD4CD25 Treg is a critical mechanism for nicotinic anti-inflammatory pathway and it may be feasible to use selective agonists as an immunotherapy for SAP.
Authors: Xiyuan Bai; Jerry A Stitzel; An Bai; Cristian A Zambrano; Matthew Phillips; Philippa Marrack; Edward D Chan Journal: Am J Respir Cell Mol Biol Date: 2017-09 Impact factor: 6.914
Authors: A A Alahmari; B Sreekumar; V Patel; M Ashat; M Alexandre; A K Uduman; E O Akinbiyi; A Ceplenski; C A Shugrue; T R Kolodecik; N Tashkandi; S W Messenger; G E Groblewski; F S Gorelick; E C Thrower Journal: PLoS One Date: 2018-06-05 Impact factor: 3.240