Protective Mechanism of MIF Inhibitor ISO-1 on Intrahepatic Bile Duct Cells in Rats with Severe Acute Pancreatitis.

Abstract

AIMS:

This study aimed to explore the protection mechanism of ISO-1 on severe acute pancreatitis-associated intrahepatic bile duct (IBD) injury in rats.

METHODS:

Forty-eight specific-pathogen-free male Wistar rats were randomly divided into four groups (N = 12): a sham operation group (SO group), a severe acute pancreatitis model group (SAP group), a ISO-1 treatment group (ISO-1 + SAP group), and a ISO-1 control group (ISO-1 + SO group). All rats were killed after 12 h of being made models. 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 SAP, after treatment with ISO-1, the pathological injuries of pancreas, liver, and IBD cells in ISO-1 treatment group remarkably relieved. The expression of MIF in the IBD cells was significantly downregulated both at mRNA and at protein levels in ISO-1 treatment group. Besides, the protein expression levels of P38, P-P38, NF-κBp65, TNF-α, IL-1β, and IL-6 in the IBD in rats were also significantly decreased in ISO-1 treatment group (all P < 0.05).

CONCLUSION:

ISO-1 may protect the IBD cells, reduce pathological injuries, and reduce the inflammatory response in SAP rats. Its mechanisms may be via inhibiting the expression of MIF and then blocking the activation of p38-MAPK and NF-κB signaling pathway.

• Authors: Bin Wang, Kailiang Zhao, Wenjuan Hu, Youming Ding, Weixing Wang
• Journal: Digestive diseases and sciences (Dig Dis Sci) Vol. 66 Issue 10 Pg. 3415-3426 (10 2021) ISSN: 1573-2568 [Electronic] United States
• PMID: 33123939 (Publication Type: Journal Article)
• Copyright: © 2020. Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• 3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazoleacetic acid methyl ester
• Cytokines
• Isoxazoles
• Macrophage Migration-Inhibitory Factors
• Intramolecular Oxidoreductases
• Mif protein, rat

Topics

• Acute Disease
• Animals
• Bile Ducts, Intrahepatic (cytology)
• Cytokines (genetics, metabolism)
• Gene Expression Regulation (drug effects)
• Intramolecular Oxidoreductases (antagonists & inhibitors, genetics, metabolism)
• Isoxazoles (pharmacology)
• Macrophage Migration-Inhibitory Factors (antagonists & inhibitors, genetics, metabolism)
• Male
• Pancreatitis (etiology, metabolism, pathology)
• Random Allocation
• Rats
• Rats, Wistar
• Real-Time Polymerase Chain Reaction
• Specific Pathogen-Free Organisms