Macrophage Migration Inhibitory Factor - A Favorable Marker in Inflammatory Diseases?

Hertelendy, Johannes; Reumuth, Georg; Simons, David; Stoppe, Christian; Kim, Bong-Sung; Stromps, Jan-Philipp; Fuchs, Paul Christian; Pallua, Norbert; Grieb, Gerrit

doi:10.2174/0929867324666170714114200

Cited by 25 publications

(16 citation statements)

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“…Earlier evidence has indicated rapid fatal outcomes in septic patients with high levels of macrophage migration inhibitory factor (MIF; Chuang et al, ), consistent with the widely accepted notion that of a provoked pro‐inflammatory response in sepsis (Magrone & Jirillo, ). MIF, a pluripotent cytokine, found in various cell types including immune, endothelial and epithelial cells, is deemed a biomarker for inflammatory diseases such as sepsis, systemic infection and autoimmune disease (Hertelendy et al, ). Nonetheless, results from our lab revealed a somewhat paradoxical role for MIF in disease settings, such as obesity and pressure overload‐induced cardiac anomalies through autophagy regulation (Xu, Hua, Nair, Bucala, & Ren, ; Xu & Ren, ).…”

Section: Introductionmentioning

confidence: 99%

CD74 knockout protects against LPS‐induced myocardial contractile dysfunction through AMPK‐Skp2‐SUV39H1‐mediated demethylation of BCLB

Luo

Fan

Yang

et al. 2020

British J Pharmacology

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Background and Purpose Lipopolysaccharides (LPS), an outer membrane component of Gram‐negative bacteria, triggers myocardial anomalies in sepsis. Recent findings indicated a role for inflammatory cytokine MIF and its receptor, CD74, in septic organ injury, although little is known of the role of MIF‐CD74 in septic cardiomyopathy. Experimental Approach This study evaluated the impact of CD74 ablation on endotoxaemia‐induced cardiac anomalies. Echocardiographic, cardiomyocyte contractile and intracellular Ca2+ properties were examined. Key Results Our data revealed compromised cardiac function (lower fractional shortening, enlarged LV end systolic diameter, decreased peak shortening, maximal velocity of shortening/relengthening, prolonged duration of relengthening and intracellular Ca2+ mishandling) and ultrastructural derangement associated with inflammation, O2− production, apoptosis, excess autophagy, phosphorylation of AMPK and JNK and dampened mTOR phosphorylation. These effects were attenuated or mitigated by CD74 knockout. LPS challenge also down‐regulated Skp2, an F‐box component of Skp1/Cullin/F‐box protein‐type ubiquitin ligase, while up‐regulating that of SUV39H1 and H3K9 methylation of the Bcl2 protein BCLB. These effects were reversed by CD74 ablation. In vitro study revealed that LPS facilitated GFP‐LC3B formation and cardiomyocyte defects. These effects were prevented by CD74 ablation. Interestingly, the AMPK activator AICAR, the autophagy inducer rapamycin and the demethylation inhibitor difenoconazole inhibited the effects of CD74 ablation against LPS‐induced cardiac dysfunction, while the SUV39H1 inhibitor chaetocin or methylation inhibitor 5‐AzaC ameliorated LPS‐induced GFP‐LC3B formation and cardiomyocyte contractile dysfunction. Conclusion and Implications Our data suggested that CD74 ablation protected against LPS‐induced cardiac anomalies, O2− production, inflammation and apoptosis through suppression of autophagy in a Skp2‐SUV39H1‐mediated mechanism.

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Section: Introductionmentioning

confidence: 99%

CD74 knockout protects against LPS‐induced myocardial contractile dysfunction through AMPK‐Skp2‐SUV39H1‐mediated demethylation of BCLB

Luo

Fan

Yang

et al. 2020

British J Pharmacology

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“…14,16 Serving as an inflammatory, chemokine-like cytokine and upstream regulator of innate immunity, it is not unexpected that MIF has a key role in numerous inflammatory and autoimmune conditions, including septic shock, rheumatoid arthritis (RA), systemic lupus erythematosus, Crohn's disease, obesity, glomerulonephritis and inflammatory and allergic lung conditions (reviewed in Refs. 15,[27][28][29][30] ). Owing to the close mechanistic links between chronic inflammation and cancer, MIF also has been identified as a pro-tumorigenic factor in several tumour entities, enhancing cancer cell proliferation, promoting tumour angiogenesis and modulating anti-tumour immunity.…”

Section: Mif Is a Chemokine-like Inflammatory Mediator That Promotes mentioning

confidence: 99%

Macrophage Migration Inhibitory Factor (MIF)-Based Therapeutic Concepts in Atherosclerosis and Inflammation

et al. 2019

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Chemokines orchestrate leukocyte recruitment in atherosclerosis and their blockade is a promising anti-atherosclerotic strategy, but few chemokine-based approaches have advanced into clinical trials, in part owing to the complexity and redundancy of the chemokine network. Macrophage migration inhibitory factor (MIF) is a pivotal mediator of atherosclerotic lesion formation. It has been characterized as an inflammatory cytokine and atypical chemokine that promotes atherogenic leukocyte recruitment and lesional inflammation through interactions with the chemokine receptors CXCR2 and CXCR4, but also exhibits phase-specific CD74-mediated cardioprotective activity. The unique structural properties of MIF and its homologue MIF-2/D-DT offer intriguing therapeutic opportunities including small molecule-, antibody- and peptide-based approaches that may hold promise as inhibitors of atherosclerosis, while sparing tissue-protective classical chemokine pathways. In this review, we summarize the pros and cons of anti-MIF protein strategies and discuss their molecular characteristics and receptor specificities with a focus on cardiovascular disease.

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“…The proinflammatory activity of MIF has been implicated in a diverse range of biological processes including activation of ERK/MAPK pathways and inhibition of the anti-inflammatory actions of glucocorticoids. MIF has also been shown to induce the production of downstream pro-inflammatory gene expression, such as TNF-α, IL-8, and IL-17 (Calandra and Roger, 2003; Larson and Horak, 2006; Hertelendy et al, 2018). MIF plays an important role in host defense against a variety of microorganisms including protozoan parasites (Satoskar et al, 2001; Calandra and Roger, 2003; Magalhaes et al, 2009; Cavalcanti et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…MIF has been demonstrated to be involved in innate and adaptive immune responses by stimulating the production of pro-inflammatory mediators, such as TNF-α and IL-8. MIF was found to sustain macrophage survival and proinflammatory function by suppressing activation-induced, p53-dependent apoptosis (Mitchell et al, 2002; Calandra and Roger, 2003; Larson and Horak, 2006; Hertelendy et al, 2018). The cytokines affected by MIF are involved in the pathogenesis of infectious and non-infectious inflammatory diseases (de Oliveira Gomes et al, 2011; Gomes et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Protective Effect Against Toxoplasmosis in BALB/c Mice Vaccinated With Toxoplasma gondii Macrophage Migration Inhibitory Factor

et al. 2019

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Toxoplasma gondii is an obligate intracellular parasite responsible for toxoplasmosis, which can cause severe disease in the fetus and immunocompromised individuals. Developing an effective vaccine is crucial to control this disease. Macrophage migration inhibitory factor (MIF) has gained substantial attention as a pivotal upstream cytokine to mediate innate and adaptive immune responses. Homologs of MIF have been discovered in many parasitic species, and one homolog of MIF has been isolated from the parasite Toxoplasma gondii. In this study, the recombinant Toxoplasma gondii MIF (rTgMIF) as a protein vaccine was expressed and evaluated by intramuscular injection in BALB/c mice. We divided the mice into different dose groups of vaccines, and all immunizations with purified rTgMIF protein were performed at 0, 2, and 4 weeks. The protective efficacy of vaccination was analyzed by antibody assays, cytokine measurements and lymphoproliferative assays, respectively. The results obtained indicated that the rTgMIF vaccine elicited strong humoral and cellular immune responses with high levels of IgG antibody and IFN-γ production compared to those of the controls, in addition to slight higher levels of IL-4 production. After vaccination, a stronger lymphoproliferative response was also noted. Additionally, the survival time of mice immunized with rTgMIF was longer than that of the mice in control groups after challenge infection with virulent T. gondii RH tachyzoites. Moreover, the number of brain tissue cysts in vaccinated mice was reduced by 62.26% compared with the control group. These findings demonstrated that recombinant TgMIF protein is a potential candidate for vaccine development against toxoplasmosis.

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Macrophage Migration Inhibitory Factor - A Favorable Marker in Inflammatory Diseases?

Abstract: Recent studies suggest MIF to be a marker for different inflammatory diseases and might serve as therapeutic target in the future.

Cited by 25 publications

References 0 publications

CD74 knockout protects against LPS‐induced myocardial contractile dysfunction through AMPK‐Skp2‐SUV39H1‐mediated demethylation of BCLB

CD74 knockout protects against LPS‐induced myocardial contractile dysfunction through AMPK‐Skp2‐SUV39H1‐mediated demethylation of BCLB

Macrophage Migration Inhibitory Factor (MIF)-Based Therapeutic Concepts in Atherosclerosis and Inflammation

Protective Effect Against Toxoplasmosis in BALB/c Mice Vaccinated With Toxoplasma gondii Macrophage Migration Inhibitory Factor

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