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Published on: May 10, 2024
Targeting Macrophage Migration Inhibitory Factor in Acute Pancreatitis and Pancreatic Cancer
Yongjian Wen1,2,3, Wenhao Cai1,4, Jingyu Yang1
1Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital of Sichuan University, Chengdu, China.
Abstract:
Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine implicated in the pathogenesis of inflammation and cancer. It is produced by various cells and circulating MIF has been identified as a biomarker for a range of diseases. Extracellular MIF mainly binds to the cluster of differentiation 74 (CD74)/CD44 to activate downstream signaling pathways. These in turn activate immune responses, enhance inflammation and can promote cancer cell proliferation and invasion. Extracellular MIF also binds to the C-X-C chemokine receptors cooperating with or without CD74 to activate chemokine response. Intracellular MIF is involved in Toll-like receptor and inflammasome-mediated inflammatory response. Pharmacological inhibition of MIF has been shown to hold great promise in treating inflammatory diseases and cancer, including small molecule MIF inhibitors targeting the tautomerase active site of MIF and antibodies that neutralize MIF. In the current review, we discuss the role of MIF signaling pathways in inflammation and cancer and summarize the recent advances of the role of MIF in experimental and clinical exocrine pancreatic diseases. We expect to provide insights into clinical translation of MIF antagonism as a strategy for treating acute pancreatitis and pancreatic cancer.
Insights
Macrophage migration inhibitory factor (MIF) is crucial in inflammation and cancer. Inhibiting MIF shows promise for treating pancreatitis and pancreatic cancer by blocking its signaling pathways.
Area of Science:
- Immunology
- Oncology
- Gastroenterology
Background:
- Macrophage migration inhibitory factor (MIF) is a cytokine involved in inflammation and cancer.
- Circulating MIF is a biomarker for various diseases.
- Extracellular MIF signals via CD74/CD44 or chemokine receptors; intracellular MIF mediates TLR and inflammasome responses.
Purpose of the Study:
- To review the role of MIF signaling in inflammation and cancer.
- To summarize recent advances in MIF's role in exocrine pancreatic diseases.
- To provide insights into MIF antagonism for treating pancreatitis and pancreatic cancer.
Main Methods:
- Literature review of MIF signaling pathways.
- Summary of experimental and clinical data on MIF in pancreatic diseases.
- Discussion of pharmacological MIF inhibition strategies.
Main Results:
- MIF signaling promotes inflammation, immune responses, and cancer progression.
- MIF antagonism, via small molecules or antibodies, is a promising therapeutic strategy.
- Recent advances highlight MIF's specific roles in exocrine pancreatic diseases.
Conclusions:
- MIF plays a significant role in the pathogenesis of inflammation and cancer.
- Targeting MIF offers a potential therapeutic avenue for acute pancreatitis and pancreatic cancer.
- Further research into MIF antagonism could lead to novel clinical treatments.
