Evolving complexity of MIF signaling

Jankauskas, Stanislovas S.; Wong, Dickson W.L.; Bucala, Richard; Djudjaj, Sonja; Boor, Peter

doi:10.1016/j.cellsig.2019.01.006

Cited by 163 publications

(158 citation statements)

References 176 publications

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“…important CNS functions and disturbances, ranging from filopodium formation, synaptogenesis, learning disability, behavioural anomalies and neuronal plasticity to neurodegenerative disorders [40]. In addition to these observations, it has been suggested that changes in the microbiota are associated with increased gut permeability and systemic inflammation that may play an important role in age-associated alteration of cognitive and behaviours in ageing [41].…”

Section: Discussionmentioning

confidence: 99%

Faecal microbiota transplant from aged donor mice affects spatial learning and memory via modulating hippocampal synaptic plasticity- and neurotransmission-related proteins in young recipients

D’Amato

Cesare-Mannelli

Lucarini

et al. 2019

Preprint

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Background. The gut-brain axis and the intestinal microbiota are emerging as key players in health and disease. Shifts in intestinal microbiota composition affect a variety of systems, however, evidence of their direct impact on cognitive functions is still lacking. We tested whether faecal microbiota transplant (FMT) from aged donor mice into young adult recipients affected the hippocampus, an area of the central nervous system (CNS) known to be affected by the ageing process, and related functions. Methods and Findings.Young adult mice were transplanted with the microbiota from either aged or age-matched donor mice. Following transplantation, characterization of the microbiotas and metabolomics profiles along with a battery of cognitive and behavioural tests were performed. Label-free quantitative proteomics was employed to monitor protein expression in the hippocampus of the recipients. Gut permeability, levels of circulating cytokines and expression of markers of microglia cells were also assessed. FMT from aged donors led to impaired spatial learning and memory in young adult recipients, whereas anxiety, explorative behaviour and locomotor activity remained unaffected. This was paralleled by altered expression of proteins involved in synaptic plasticity and neurotransmission in the hippocampus. Also, a strong reduction of bacteria associated with short-chain fatty acids (SCFAs) production (Lachnospiraceae, Faecalibaculum, and Ruminococcaceae) and disorders of the CNS (Prevotellaceae and Ruminococcaceae) was observed. Finally, microglia cells of the hippocampus fimbria, acquired an ageing-like phenotype, while gut permeability and levels of circulating cytokines remained unaffected. Conclusions.These results demonstrate a direct effect of the age-associated shifts of the microbiota on protein expression and key functions of the central nervous system. Furthermore, these results additionally highlight the paramount importance of the gut-brain axis in ageing and provide a strong rationale to devise therapies aiming to restore a younglike microbiota to improve cognitive functions in the elderly.

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Section: Discussionmentioning

confidence: 99%

Faecal microbiota transplant from aged donor mice affects spatial learning and memory via modulating hippocampal synaptic plasticity- and neurotransmission-related proteins in young recipients

D’Amato

Cesare-Mannelli

Lucarini

et al. 2019

Preprint

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“…19 The promoter sequence of MIF has several specific binding sites for different transcription factors that regulate its expression, which include SP1, CREB, NFkB, Pit-1, AP-1, ICBP90, and HIF-1α. [20][21][22][23][24] The first functional variant of MIF is a single nucleotide polymorphism at -173 (G > C), which creates a binding site for protein activator-4 (AP4) that increases promoter activity of MIF. 21 The second site consists of the CATT repeats at -794 which repeats 5-8 times, creating a binding site for the transcriptional factor Pit-1, as well as ICBP90, which regulates the activity on this site.…”

Section: Introductionmentioning

confidence: 99%

Association of the genetic variants (‐794 CATT5‐8 and ‐173 G > C) of macrophage migration inhibitory factor (MIF) with higher soluble levels of MIF and TNFα in women with breast cancer

Avalos‐Navarro

Toro-Arreola

Daneri-Navarro

et al. 2020

Clinical Laboratory Analysis

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Background: Functional variants -173 G > C (rs755622) and -794CATT 5-8 (rs5844572) MIF gene have been associated with the risk in several types of cancer, as well as with the increase of soluble levels of MIF and TNFα. However, in previous studies contradictory and uncertain results have been presented on the implication of MIF polymorphisms with the association in cancer, specifically in breast cancer (BC). We investigated whether the variants are associated with the susceptibility to develop BC and the soluble levels of MIF and TNFα in women with BC from western Mexico. Materials and methods:A total of 152 women with BC and 182 control subjects (CS) were enrolled in this study. The determination of genotypes -173 G > C and -794 CATT 5-8 MIF polymorphisms was performed by PCR-RFLP and PCR, respectively. In addition, the soluble levels of MIF and TNFα in both studied groups were quantified by ELISA and MILLIPLEX assay, respectively. Results:The most frequent allele found in BC was the G (74.3%) and 6 (54%) in the variants -173G > C and -794 CATT 5-8 , respectively, without significant differences in both groups. Nevertheless, the women with BC carriers -173*C and -794CATT 7 have higher levels of MIF in comparison with CS. An increase of MIF (BC: 11.1 ng/mL vs CS: 5.2 ng/mL, P < .001) and TNFα (BC: 24.9 ng/mL vs CS: 9.9 pg/mL, P < .001) was found. Conclusion:The functional variants of MIF are not genetic susceptibility markers for BC. Nevertheless, the alleles -173*C and -794CATT 7 are associated with the increase of MIF circulating in women with BC.

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“…It has also been observed that MIF promotes the survival of macrophages by inhibiting p53e [5]. However, like for several other cytokines, pleiotropic effects have also been described for MIF that, under certain circumstances, may promote type 2 anti-inflammatory responses that seem to be primarily mediated by its ability to activate the AMPK pathway [3,5,6].…”

Section: Macrophage Migration Inhibitory Factor (Mif)mentioning

confidence: 99%

The Dichotomic Role of Macrophage Migration Inhibitory Factor in Neurodegeneration

Basile

Battaglia

Bruno

et al. 2020

IJMS

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Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine expressed by different cell types and exerting multiple biological functions. It has been shown that MIF may be involved in several disorders, including neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), Parkinson disease (PD), and Huntington disease (HD), that represent an unmet medical need. Therefore, further studies are needed to identify novel pathogenetic mechanisms that may translate into tailored therapeutic approaches so to improve patients’ survival and quality of life. Here, we reviewed the preclinical and clinical studies investigating the role of MIF in ALS, PD, and HD. The emerging results suggest that MIF might play a dichotomic role in these disorders, exerting a protective action in ALS, a pathogenetic action in HD, and a yet undefined and debated role in PD. The better understanding of the role of MIF in these diseases could allow its use as a novel diagnostic and therapeutic tool for the monitoring and treatment of the patients and for eventual biomarker-driven therapeutic approaches.

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Evolving complexity of MIF signaling

Cited by 163 publications

References 176 publications

Faecal microbiota transplant from aged donor mice affects spatial learning and memory via modulating hippocampal synaptic plasticity- and neurotransmission-related proteins in young recipients

Faecal microbiota transplant from aged donor mice affects spatial learning and memory via modulating hippocampal synaptic plasticity- and neurotransmission-related proteins in young recipients

Association of the genetic variants (‐794 CATT5‐8 and ‐173 G > C) of macrophage migration inhibitory factor (MIF) with higher soluble levels of MIF and TNFα in women with breast cancer

The Dichotomic Role of Macrophage Migration Inhibitory Factor in Neurodegeneration

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