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Macrophage Migration Inhibitor Promoted the Intrahepatic Bile Duct Injury in Rats with Severe Acute Pancreatitis

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Abstract

Background

Macrophage migration inhibitory factor (MIF) is involved in many acute and chronic inflammatory diseases. However, its role in intrahepatic bile duct (IBD) cell damage associated with severe acute pancreatitis (SAP) remains unclear.

Aims

This study was aimed to identify the role of MIF and its underlying mechanisms in SAP complicated by IBD cell damage.

Methods

Forty-eight specific-pathogen-free male Wistar rats were randomly divided into four groups (N = 12): a sham operation group (SO group) and three SAP model groups (SAP-3h, SAP-6h, and SAP-12h). Immunohistochemistry was used to detect the expression of MIF and P38 in IBD cells. MIF mRNA expression in IBD cells was observed using real-time fluorescent quantitative polymerase chain reaction (real-time PCR). In addition, Western blotting was performed to detect the protein expression of P38, phosphorylated P38 (P-P38), nuclear factor-κB (NF-κB p65), and tumor necrosis factor alpha (TNF-α). Enzyme-linked immunosorbent assays were used to analyze the levels of TNF-α, IL-1β, and IL-6 in the IBD of rats.

Results

Compared with the SO group, the expression of MIF in the IBD was significantly upregulated both at mRNA and at protein levels in the SAP group. Besides, the protein expression levels of P38, P-P38, NF-κB, p65, TNF-α, IL-1β, and IL-6 in the IBD in rats were also significantly increased in the SAP group and the levels increased gradually as acute pancreatitis progressed (all P < 0.05).

Conclusions

MIF may promote the IBD injury and inflammatory reaction in SAP via activating the P38-MAPK and NF-κB signaling pathways.

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Abbreviations

MIF:

Macrophage migration inhibitory factor

SAP:

Severe acute pancreatitis

IBD:

Intrahepatic bile duct

SPF:

Specific pathogen-free

SO:

Sham operation

NF-κB:

Nuclear factor-κB

TNF:

Tumor necrosis factor

ELISA:

Enzyme-linked immunosorbent assays

IL:

Interleukin

MODS:

Multiple organ dysfunction syndrome

MOF:

Multiple organ failure

SIRS:

Systemic inflammatory response syndrome

ARDS:

Acute respiratory distress syndrome

AP:

Acute pancreatitis

MAPK:

Mitogen-activated protein kinase

ICAM:

Intercellular adhesion molecule

VCAM:

Vascular cell adhesion protein

MCP:

Monocyte chemoattractant protein

HRP:

Horseradish peroxidase

H&E:

Hematoxylin and eosin

PBS:

Phosphate-buffered saline

IOD:

Integral optical density

SEM:

Standard error of the mean

OD:

Optical density

PL:

Phospholipase

PAF:

Platelet-activating factor

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Acknowledgments

The authors would like to thank professor Mingxia Fan, the director of experiment animal central of Renmin hospital of Wuhan university, for whose technical assistance and contribute to animal feeding and model making, and specimen collection.

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Authors and Affiliations

  1. Department of Hepatobiliary and Laparoscopic Surgery, Renmin Hospital, Wuhan University, Hubei Key Laboratory of Digestive System Disease, Wuhan, 430060, Hubei Province, China

    Bin Wang, Kai-Liang Zhao, You-Ming Ding & Wei-Xing Wang

  2. Department of Anesthesiology, Renmin Hospital, Wuhan University, Wuhan, 430060, Hubei Province, China

    Wen-Juan Hu

  3. Department of Gastrointestinal Surgery, Renmin Hospital, Wuhan University, Hubei Key Laboratory of Digestive System Disease, Wuhan, 430060, Hubei Province, China

    Teng Zuo

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  1. Bin Wang
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  2. Kai-Liang Zhao
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Correspondence to Bin Wang.

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Wang, B., Zhao, KL., Hu, WJ. et al. Macrophage Migration Inhibitor Promoted the Intrahepatic Bile Duct Injury in Rats with Severe Acute Pancreatitis. Dig Dis Sci 64, 759–772 (2019). https://doi.org/10.1007/s10620-018-5379-7

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  • DOI: https://doi.org/10.1007/s10620-018-5379-7

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