Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 14, 2024; 30(42): 4544-4556
Published online Nov 14, 2024. doi: 10.3748/wjg.v30.i42.4544
Transfection of 12/15-lipoxygenase effectively alleviates inflammatory responses during experimental acute pancreatitis
Hong-Wei Sun, Yong-Yu Bai, Zhen-Liu Qin, Ri-Zhao Li, Tinotenda Blessing Madzikatire, Percy David Papa Akuetteh, Qiang Li, Hong-Ru Kong, Yue-Peng Jin
Hong-Wei Sun, Yong-Yu Bai, Qiang Li, Hong-Ru Kong, Yue-Peng Jin, National Key Clinical Specialty (General Surgery), The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
Zhen-Liu Qin, Ri-Zhao Li, Tinotenda Blessing Madzikatire, Percy David Papa Akuetteh, Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
Co-first authors: Hong-Wei Sun and Yong-Yu Bai.
Author contributions: Jin YP designed the study and supervised the study; Sun HW and Bai YY wrote the article and performed the experiments; Qin ZL and Li RZ performed the experiments; Madzikatire TB and Akuetteh PDP assisted with the article correction; Li Q and Kong HR analyzed the data. Sun HW and Bai YY contributed equally to this work as co-first authors.
Supported by National Health Commission Research Fund, No. WKJ-ZJ-2342; National Natural Science Foundation of China, No. 81900583; and Science and Technology Plan Project of Wenzhou, No. Y20180103.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of Wenzhou Medical University.
Institutional animal care and use committee statement: The Institutional Animal Committee of Wenzhou Medical University, Wenzhou, China, approved the protocol for the animal experiment. All animals received care as prescribed under the ‘Guide for the Care and Use of Laboratory Animals’.
Conflict-of-interest statement: All authors have no conflicts of interest to declare.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yue-Peng Jin, PhD, Associate Chief Physician, National Key Clinical Specialty (General Surgery), The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang Street, Wenzhou 325000, Zhejiang Province, China. quiet1981@163.com
Received: March 27, 2024
Revised: August 26, 2024
Accepted: October 8, 2024
Published online: November 14, 2024
Processing time: 218 Days and 7.5 Hours
Abstract
BACKGROUND

Acute pancreatitis (AP), the initially triggered inflammatory process in the pancreas, can be life-threatening. It has been reported that 15-lipoxygenase may promote the removal of damaged intracellular components, maintain intracellular homeostasis, and promote apoptosis by upregulating the activity of caspases. Despite an increased understanding of the lipoxygenase pathway in inflammation and immune diseases, the role of the Alox15 gene product in modulating the inflammatory changes during AP is not well defined.

AIM

To investigate the effect of Alox15 expression in cerulein-induced AP in rats.

METHODS

Model rats were transfected with Alox15 by injecting a recombinant lentivirus vector encoding Alox15 into the left gastric artery before inducing AP. The expression of Alox15 was then assessed at the mRNA and protein levels.

RESULTS

Our in vivo results showed that serum amylase activity and pancreatic tissue water content were significantly reduced in Alox15-transfected rats. Further, the mRNA expression levels of tumor necrosis factor alpha, interleukin (IL)-1β, IL-6, and monocyte chemoattractant protein-1, as well as the protein expression of nuclear factor kappa B in pancreatic tissue were reduced. Additionally, we observed an upregulation of cleaved caspase-3 that implies an induction of apoptosis in pancreatic cells. The transfection of Alox15 resulted in a lower number of autophagic vacuoles in AP.

CONCLUSION

Our findings demonstrate a regulatory role of Alox15 in apoptosis and autophagy, making it a potential therapeutic target for AP.

Keywords: Acute pancreatitis; Cerulein; 12/15-lipoxygenase; Apoptosis; Autophagy

Core Tip: Our in vivo data demonstrated for the first time that Alox15 transfection attenuated cerulein-induced acute pancreatitis (AP) in a murine model, highlighting its regulatory role in inflammation, apoptosis, and autophagy. These findings suggested that Alox15 may serve as a potential therapeutic target for the treatment of AP by modulating the key cellular processes involved in the pathology of this disease.