Nicotine ameliorates experimental severe acute pancreatitis via enhancing immunoregulation of CD4+ CD25+ regulatory T cells.
Słowa kluczowe
Abstrakcyjny
OBJECTIVE
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.
