Macrophage migration inhibitory factor (MIF) is a pleiotropic inflammatory molecule with both cytokine and noncytokine activity. MIF is constitutively released from multiple cell types via an unconventional secretory pathway that is not well defined. Here, we looked at MIF release from human and mouse monocytes/macrophages in response to different stimuli. While MIF release was not significantly altered in response to lipopolysaccharide or heat-killed Escherichia coli, cytotoxic stimuli strongly promoted release of MIF. MIF release was highly upregulated in cells undergoing necrosis, necroptosis and NLRP3 inflammasome-dependent pyroptosis. Our data suggest that cell death represents a major route for MIF release from myeloid cells. The functional significance of these findings and their potential importance in the context of autoimmune and inflammatory diseases warrant further investigation.
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http://dx.doi.org/10.1111/imcb.12376 | DOI Listing |
Cell Commun Signal
January 2025
Department of Musculoskeletal Tumor, Peking University People's Hospital, No. 11 Xizhimen South Street, Beijing, 100044, China.
Background: Ewing's sarcoma (EwS), a common pediatric bone cancer, is associated with poor survival due to a lack of therapeutic targets for immunotherapy or targeted therapy. Therefore, more effective treatment options are urgently needed.
Methods: Since novel immunotherapies may address this need, we performed an integrative analysis involving single-cell RNA sequencing, cell function experiments, and humanized models to dissect the immunoregulatory interactions in EwS and identify strategies for optimizing immunotherapeutic efficacy.
Diabet Med
December 2024
Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter Medical School, Exeter, UK.
Aims: Acute hypoglycaemia promotes pro-inflammatory cytokine production, increasing the risk for cardiovascular events in diabetes. AMP-activated protein kinase (AMPK) is regulated by and influences the production of pro-inflammatory cytokines. We sought to examine the mechanistic role of AMPK in low glucose-induced changes in the pro-inflammatory cytokine macrophage migration inhibitory factor (MIF), which is elevated in people with diabetes.
View Article and Find Full Text PDFInt J Mol Sci
November 2024
Department of Digestive Tract Diseases, Medical University of Lodz, 90-153 Lodz, Poland.
Disturbances in carbohydrate metabolism are suggested to be the early symptoms of pancreatic ductal adenocarcinoma (PDAC). The accumulated data suggests that endocrine function-related biomarkers may represent a breakthrough in the early detection of PDAC. Factors which may predispose one to the development of PDAC are insulin resistance and hyperinsulinemia.
View Article and Find Full Text PDFPLoS Biol
November 2024
Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel.
CD74 is a cell-surface receptor for the cytokine macrophage migration inhibitory factor (MIF). MIF binding to CD74 induces a signaling cascade resulting in the release of its cytosolic intracellular domain (CD74-ICD), which regulates transcription in naïve B and chronic lymphocytic leukemia (CLL) cells. In the current study, we investigated the role of CD74 in the regulation of the immunosuppressive tumor microenvironment (TME) in triple-negative breast cancer (TNBC).
View Article and Find Full Text PDFBladder (San Franc)
October 2024
Lexington VA Health Care System, Research and Development, Lexington, KY, USA.
Background: Repeated intravesical activation of protease-activated receptor-4 (PAR4) serves as a model of persistent bladder hyperalgesia (BHA) in mice, which lasts several days after the final stimulus. Spinal macrophage migration inhibitory factor (MIF) and high mobility group box 1 (HMGB1) are critical mediators in the persistence of BHA.
Objective: We aimed to identify effective systemic treatments for persistent BHA using antagonists or transgenic deletions.
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