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

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.

journal_name

Pancreas

journal_title

Pancreas

authors

Zheng YS,Wu ZS,Zhang LY,Ke L,Li WQ,Li N,Li JS

doi

10.1097/MPA.0000000000000294

subject

Has Abstract

pub_date

2015-04-01 00:00:00

pages

500-6

issue

3

eissn

0885-3177

issn

1536-4828

journal_volume

44

pub_type

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