Macrophage migration inhibitory factor in inflammasome formation and macrophage recruitment in cervical cell carcinoma
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ABSTRACT:
PROVIDER: PRJNA1180112 | ENA |
REPOSITORIES: ENA
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Project description:Despite the demonstrated efficacy of immune checkpoint blockade therapies in various tumors, their efficacy in cervical cancer is limited by factors such as the need for positive PD-L1 expression and the development of drug resistance. A crucial pro-inflammatory cytokine, macrophage migration inhibitory factor (MIF), is highly expressed in various cancers and contributes to tumor progression by regulating inflammatory responses and the tumor microenvironment. The present study aimed to explore the role of macrophage migration inhibitory factors in cervical squamous cell carcinoma (CSCC) recurrence and metastasis. Western blotting, reverse transcription quantitative PCR, cell-counting kit 8 assay, flow cytometry, and ELISA were used to investigate the effects of MIF on CSCC progression and formation of inflammasomes. Transcriptome and proteome sequencing were combined to screen for key effector proteins of MIF. Moreover, in vitro co-culture experiments, Transwell assays, and flow cytometry were used to evaluate the roles of MIF and TSC22 domain family protein 3 (TSC22D3) as inflammatory tumor-promoting factors in macrophage recruitment and polarization induction. The results indicated that MIF was highly expressed in CSCC with lymph node metastasis, positively correlated with cervical cancer stage, and associated with poor prognosis. MIF was found to promote CSCC progression and linked to inflammasome activation. Multi-omics screening results indicated that TSC22D3 may be a crucial interacting gene of MIC. Moreover, MIF and TSC22D3 could facilitate inflammasome activation, macrophage recruitment, and M2 polarization. Therefore, MIF and TSC22D3 can induce macrophage infiltration in cervical cancer lesions and affect the tumor microenvironment by polarizing macrophages toward the M2 phenotype, promoting CSCC progression. This study highlights the potential of targeting the MIF-TSC22D3 axis as a novel therapeutic strategy and offering a promising avenue for improving the efficacy of immunotherapy in treatin
2025-01-26 | PXD057462 | Pride
Project description:The present study aimed to explore the role of macrophage migration inhibitory factors in cervical squamous cell carcinoma (CSCC) recurrence and metastasis.
2025-01-24 | GSE280733 | GEO
Project description:Firstly, the adductome of he protein macrophage migration inhibitory factor (MIF) with different haptens encompassing different reaction mechanisms and potencies was investigated. After incubation of MIF with the different haptens at 5 times molar excess of hapten, an untargeted Full MS/dd-MS2 experimental approach was used with a QExactive Quadrupole-Orbitrap mass spectrometer. The data were processed with Proteome Discoverer and the suggested sites of adductions were confirmed in parallel reaction monitoring mode (PRM) on the same instruments.
2022-03-18 | PXD031793 | Pride
Project description:Firstly, the adductome of the two major mouse blood proteins, as well as of the protein macrophage migration inhibitory factor (MIF) with the model hapten tetramethylrhodamine isothiocyanate (TRITC)was invastigated. After incubation at different molar ratios of TRITC, an untargeted Full MS/dd-MS2 experimental approach was used with a QExactive Quadrupole-Orbitrap mass spectrometer. The data were processed with Proteome Discoverer and the suggested sites of adductions were confirmed in parallel reaction monitoring mode (PRM) on the same instruments. Blood and lymph node samples of mise treated topically with the same hapten were screened for the peptides containing the most reactive sites of the aformentioned proteins. Only the adducted N-terminal peptide of the protein MIF could be detected. Thereafter, a quantification approach in PRM mode using standards was implemented to quantify this peptide, both modified and unmodified. Quantification was based in characteristic b and y ions.
2022-04-08 | PXD031143 | Pride
Project description:The presence of activated pancreatic stellate cells (PSCs) in the pancreatic ductal adenocarcinoma (PDAC) microenvironment plays a significant role in cancer progression. Macrophage migration inhibitory factor (MIF) is overexpressed in PDAC tissues and expressed by both cancer and stromal cells. The expression status of MIF and its receptors in PDAC- associated fibroblasts or PSCs and its pathophysiological roles are yet to be elucidated. The next-generation sequencing technique was adapted to check the effect of MIF absence on the expression of other genes in mice (mPSCs).
2022-09-28 | E-MTAB-9392 | biostudies-arrayexpress
Project description:Inflammasomes are intracellular innate immune sensors that respond to pathogen and damage-associated signals with the proteolytic cleavage of caspase-1, resulting in IL-1_ and IL-18 secretion and macrophage pyroptosis. The discovery that heterozygous gain-of-function mutations in NLRP3 lead to oversecretion of IL-1_ and cause the autoinflammatory disease spectrum Cryopyrin Associated Periodic Syndrome (CAPS), led to the successful use of IL-1 blocking therapies1. We found that a de novo missense mutation in the regulatory domain of the NLRC4 (IPAF, CARD12) inflammasome causes early-onset recurrent fever flares and Macrophage Activation Syndrome (MAS). Functional analyses demonstrated spontaneous production of the inflammasome-dependent cytokines IL-1² and IL-18 exceeding levels in CAPS patients. The NLRC4 mutation led to constitutive caspase-1 cleavage in transduced cells and enhanced spontaneous production of IL-18 by both patient and NLRC4 mutant macrophages. Thus, we describe a novel monoallelic inflammasome defect that expands the autoinflammatory paradigm to include MAS and suggests novel targets for therapy. Whole blood RNA-seq from seven timepoints of one patient with NLRC4-MAS as compared to five healthy pediatric controls, 7 NOMID patients with active disease prior to anakinra treatment and the same 7 NOMID patients with inactive disease after anakinra treatment. Please note that seven time points are chronologic time point. They are ordinal, in that "1" was drawn before "2", but the distance in time between points is not constant. Thus, time points 4 through 7 correspond to samples drawn while the patient was well AND on treatment. However there may be differences between 4 and 7 pertaining to the length of treatment, and for that reason any of these samples were not considered replicates.
2014-09-08 | E-GEOD-57253 | biostudies-arrayexpress
Project description:Macrophage migration inhibitory factor (MIF) exerts multiple effects on immune cells, as well as having functions outside the immune system. MIF can promote inflammation through the induction of other cytokines, including TNF, IL-6, and IL-1 family cytokines. Here, we show that inhibition of MIF regulates the release of IL-1?, IL-1?, and IL-18, not by affecting transcription or translation of these cytokines, but via activation of the NLRP3 inflammasome. MIF is required for the interaction between NLRP3 and the intermediate filament protein vimentin, which is critical for NLRP3 activation. Further, we demonstrate that MIF interacts with NLRP3, indicating a role for MIF in inflammasome activation independent of its role as a cytokine. These data advance our understanding of how MIF regulates inflammation and identify it as a factor critical for NLRP3 inflammasome activation.
| S-EPMC5993818 | biostudies-other
Project description:Role of Macrophage migration inhibitory factor (MIF) in pancreatic stellate cells (PSCs)
| PRJEB39522 | ENA
Project description:Macrophage migration inhibitory factor is overproduced through EGR1 in TET2low resting monocytes
| PRJNA779713 | ENA
Project description:Inflammasomes are intracellular innate immune sensors that respond to pathogen and damage-associated signals with the proteolytic cleavage of caspase-1, resulting in IL-1_ and IL-18 secretion and macrophage pyroptosis. The discovery that heterozygous gain-of-function mutations in NLRP3 lead to oversecretion of IL-1_ and cause the autoinflammatory disease spectrum Cryopyrin Associated Periodic Syndrome (CAPS), led to the successful use of IL-1 blocking therapies1. We found that a de novo missense mutation in the regulatory domain of the NLRC4 (IPAF, CARD12) inflammasome causes early-onset recurrent fever flares and Macrophage Activation Syndrome (MAS). Functional analyses demonstrated spontaneous production of the inflammasome-dependent cytokines IL-1² and IL-18 exceeding levels in CAPS patients. The NLRC4 mutation led to constitutive caspase-1 cleavage in transduced cells and enhanced spontaneous production of IL-18 by both patient and NLRC4 mutant macrophages. Thus, we describe a novel monoallelic inflammasome defect that expands the autoinflammatory paradigm to include MAS and suggests novel targets for therapy.
2014-09-08 | GSE57253 | GEO