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Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by elevated levels of pro-inflammatory cytokines, such as interleukin (IL)-6, IL-17, and macrophage migration inhibitory factor (MIF). MIF induces IL-17 secretion and MIF promoter polymorphisms influence the expression of selected downstream mediators. The aim of this study was to investigate the relationship between known functional MIF haplotypes and Th17-related cytokine secretion profile in peripheral blood mononuclear cells (PBMC) from control subjects (CS) and RA patients stimulated with lipopolysaccharide (LPS) and recombinant human MIF (rhMIF). The -794 CATT and -173G > C polymorphisms of the MIF gene were determined by conventional PCR and PCR-RFLP, respectively. The most frequent haplotypes of the MIF polymorphism and PBMC were identified from three subjects homozygous for each haplotype and in both study groups, the PBMC were obtained and stimulated with LPS or rhMIF. The secretion of cytokines related to the Th17 profile was determined by a multiplex immunoassay (MAGPIX). LPS stimulation induced the secretion of cytokines related to the Th17 profile in PBMC from CS and RA patients, whereas, rhMIF only stimulated this response in PBMC from RA patients. PBMC from CS carriers of the MIF 7C haplotype showed more IL-17A, IL-17F, IL-22, and IL-23 secretion than non-7C carriers after LPS stimulation. In the case of rhMIF stimulation, the PBMC from CS carriers of the 7C haplotype secreted more IL-17A and IL-23 than non-7C carriers. In conclusion, genetic variants of the MIF promoter modulate the secretion of cytokines related to the Th17 profile in PBMC from CS inducing a differential response in comparison to PBMC from RA patients.
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http://dx.doi.org/10.1016/j.cyto.2018.11.014 | DOI Listing |
J Immunother Cancer
December 2024
Department of Pathology, Shunde Hospital of Southern Medical University, Foshan, Guangdong, China
Objective: Although immune checkpoint blockade (ICB) therapy represents a bright spot in antitumor immunotherapy, its clinical benefits in colorectal cancer (CRC) are limited. Therefore, a new target for mediating CRC immunosuppression is urgently needed. Adenomatous polyposis coli (APC) mutations have been reported as early-stage characteristic events in CRC, but the role of truncated APC in the CRC immune microenvironment remains unclear and its clinical significance has yet to be explored.
View Article and Find Full Text PDFMol Med
November 2024
Department of Laboratory Medicine, The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Foshan, Guangdong, 528200, China.
Rheumatoid arthritis (RA) is a common autoimmune disease that can lead to irreversible joint damage when it occurs, but its pathogenesis has not yet been elucidated. In this study, we explored the roles of macrophage migration inhibitory factor (MIF), endoplasmic reticulum stress (ER stress), and Th17 cells in the pathogenesis of RA. We have preliminarily confirmed that MIF expression in CD4T cells and the proportion of Th17 cells are increased in active RA patients.
View Article and Find Full Text PDFInt J Biol Macromol
November 2024
School of Breeding and Multiplication (Sanya institute of Breeding and Multiplication), Hainan University, Sanya 572025, China; School of Tropical Agriculture and Forestry, Hainan University, Haikou 570228, China. Electronic address:
The production of cassava (Manihot esculenta Crantz) is constantly threatened by cassava bacterial blight (CBB), caused by Xanthomonas phaseoli pv. manihotis (Xpm). Zinc finger-homeodomain (ZF-HD) belongs to a family of homozygous heterotypic cassette genes widely implicated in various developmental and physiological processes in plants.
View Article and Find Full Text PDFCell Biochem Biophys
December 2024
Department of General Surgery, Chongqing University Central Hospital (Chongqing Emergency Medical Center), Chongqing, China.
Colorectal cancer is one of the most common malignant tumors worldwide, with high incidence and mortality rates making it a focus of research. Chemotherapy is a primary treatment modality for colon cancer, but chemotherapy resistance severely impacts treatment efficacy. MIF has been found to promote tumor progression and resistance in various cancers.
View Article and Find Full Text PDFJ Biol Chem
July 2024
Department of Medicine, Yale School of Medicine, New Haven, Connecticut, USA. Electronic address:
Functional variants of the gene for the cytokine macrophage migration inhibitory factor (MIF) are defined by a 4-nucleotide promoter microsatellite (-794 CATT, rs5844572) and confer risk for autoimmune, infectious, and oncologic diseases. We describe herein the discovery of a prototypic, small molecule inhibitor of MIF transcription with selectivity for high microsatellite repeat number and correspondingly high gene expression. Utilizing a high-throughput luminescent proximity screen, we identify 1-carbomethoxy-5-formyl-4,6,8-trihydroxyphenazine (CMFT) to inhibit the functional interaction between the transcription factor ICBP90 (namely, UHRF1) and the MIF -794 CATT promoter microsatellite.
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