Cell Biochemistry and Biophysics

, Volume 71, Issue 2, pp 765–776 | Cite as

Role of Liver in Modulating the Release of Inflammatory Cytokines Involved in Lung and Multiple Organ Dysfunction in Severe Acute Pancreatitis

  • Yilin Wang
  • Weiyan Liu
  • Xiqiang Liu
  • Meng Sheng
  • Yaofei Pei
  • Ruoqing Lei
  • Shengdao Zhang
  • Ran Tao
Original Paper

Abstract

The objective of this study was to understand the role of liver in modulating remote organ dysfunction during severe acute pancreatitis (SAP). We used sodium taurocholate and endotoxin to induce SAP in the rats and confirmed the development of this condition by measuring serum and ascite levels of the biomarkers of liver and lung damage. Our results showed that expression of tumor necrosis factor (TNF)-α was up-regulated sequentially, first in the gut, then in the liver, and finally in lung. Moreover, the SAP-induced increase in the expressions of TNF-α and IL-6 occurring in gut, liver, and lung was directly related to the increase in time. However, in liver and lung, the transcriptional activity of NF-κB and expression of TNF-α at 4 and 8 h were not increased. The distribution sequence of the pro-inflammatory cytokines to various organs was determined by their detection in the blood from portal vein and inferior vena cava. Although liver received TNF-α during 0.5–8 h of the SAP induction, the release of this cytokine into vena cava was not increased in this period of time. In conclusion, our results suggest that the aggravation of SAP leading to development of MODS exhibited the gut-liver-lung cytokine axis. Furthermore, this study indicates that liver performs both protective and stimulatory activities in the modulation of pro-inflammatory cytokine generation and their distribution to remote organs, such as lungs.

Keywords

Pancreatitis Hepatic function Inflammatory cytokine release NF-κB Endotoxin translocation 

Abbreviations

ALT

Alanine transaminase

ARDS

Acute respiratory distress syndrome

COX-2

Cyclooxygenase-2

DAO

Diamine oxidase

DTT

Dithiothreitol

EDTA

Ethylenediamine tetraacetic acid

EMSA

Electrophoretic mobility shift assay

ESAP

Early severe acute pancreatitis

FAP

Fulminant acute pancreatitis

TNF-α

Tumor necrosis factor α

GdCl3

Gadolinium chloride

HEPES

Hydroxyethyl piperazine ethanesulfonic acid

IL-6

Interleukin 6

LPS

Lipopolysaccharide

MODS

Multiple organ dysfunction syndrome

MOF

Multi-organ failure

PDTC

Pyrrolidine dithiocarbamate

PMSF

Phenylmethylsulfonyl fluoride

SAP

Severe acute pancreatitis

SD rat

Sprague–Dawley rat

SIRS

Systemic inflammatory response syndrome

The SO Group

The sham operation group

SP

Streptomycin avidin-peroxidase

Notes

Acknowledgments

This work was supported by a National Science Foundation Grant 81001324 (to RT), PhD site special research Grant from Ministry of Education 20100073120094 (to RT), “SMC-Rising Star Funding” from Shanghai Jiaotong University (to RT), and Endowed Professorship (“Oriental Scholar”) funding from Shanghai Municipal Science and Technology Committee (to RT).

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Yilin Wang
    • 1
    • 2
  • Weiyan Liu
    • 2
  • Xiqiang Liu
    • 1
  • Meng Sheng
    • 1
  • Yaofei Pei
    • 1
  • Ruoqing Lei
    • 1
  • Shengdao Zhang
    • 1
  • Ran Tao
    • 1
  1. 1.Center for Organ Transplantation and Department of Surgery, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghaiChina
  2. 2.Department of SurgeryMinhang District Central HospitalShanghaiChina

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