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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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