Macrophage migration inhibitory factor enhances influenza-associated mortality in mice

Smith, Candice A.; Tyrell, Daniel J.; Kulkarni, Upasana; Wood, Sherri C.; Leng, Lin; Zemans, Rachel L.; Bucala, Richard; Goldstein, Daniel R.

doi:10.1172/jci.insight.128034

Cited by 18 publications

(21 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been suggested that the level of MIF expression can be regarded as a sensitive and effective biochemical indicator in the early diagnosis of ARDS [19]. Also, MIF has been identified in some viral infections like influenza, Human Immunodeficiency Virus (HIV), H5N1 virus and dengue virus infections [20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Does Macrophage Migration Inhibitory Factor predict the prognosis of COVID-19 disease?

Dheir

Yaylacı

Sipahi

et al. 2021

J Infect Dev Ctries

View full text Add to dashboard Cite

Introduction: The aim of this study is to investigate whether macrophage migration inhibitory factor (MIF) predicts the prognosis of COVID-19 disease. Methodology: This descriptive and cross-sectional study was conducted on 87 confirmed COVID-19 patients. The patients were separated into two groups according to the admission in the ICU or in the ward. MIF was determined batchwise in plasma obtained as soon as the patients were admitted. Both groups were compared with respect to demographic characteristics, biochemical parameters and prediction of requirement to ICU admission. Results: Forty seven patients in ICU, and 40 patients in ward were included. With respect to MIF levels and biochemical biomarkers, there was a statistically significant difference between the ICU and ward patients (p< 0.024). In terms of ICU requirement, the cut-off value of MIF was detected as 4.705 (AUC:0.633, 95%CI:0.561-0.79, p= 0.037), D-dimer was 789 (AUC:0.779, 95%CI: 0.681-0.877, p= 0.000), troponin was 8.15 (AUC: 0.820, 95%CI:0.729-0.911, p= 0.000), ferritin was 375 (AUC: 0.774, 95%CI:0.671-0.876, p= 0.000), and lactate dehydrogenase (LDH) was 359.5 (AUC:0.843, 95%CI: 0.753-0.933, p= 0.000). According to the logistic regression analysis; when MIF level > 4.705, the patient’s requirement to ICU risk was increased to 8.33 (95%CI: 1.73-44.26, p= 0.009) fold. Similarly, elevation of troponin, ferritin and, LDH was shown to predict disease prognosis (p< 0.05). Conclusions: Our study showed that MIF may play a role in inflammatory responses to COVID-19 through induction of pulmonary inflammatory cytokines, suggesting that pharmacotherapeutic approaches targeting MIF may hold promise for the treatment of COVID-19 pneumonia.

show abstract

Section: Introductionmentioning

confidence: 99%

Does Macrophage Migration Inhibitory Factor predict the prognosis of COVID-19 disease?

Dheir

Yaylacı

Sipahi

et al. 2021

J Infect Dev Ctries

View full text Add to dashboard Cite

show abstract

“…Besides parasitic and bacterial models, in which MIF was shown to drive/mediate infection-related immune-pathological outcomes, analogous MIF-mediated effects were also documented to occur during experimental viral infections. For example, influenza A virus (IAV) infections in Mif -/- mice resulted in less inflammation, viral load and mortality compared to WT control mice and similar features were recorded with antibody-mediated MIF blockade ( 133 ). Conversely, transgenic mice overexpressing MIF in alveolar epithelial cells had higher inflammation, viral load, and mortality ( 133 ).…”

Section: Macrophage Migration Inhibitory Factor (Mif)mentioning

confidence: 90%

“…For example, influenza A virus (IAV) infections in Mif -/- mice resulted in less inflammation, viral load and mortality compared to WT control mice and similar features were recorded with antibody-mediated MIF blockade ( 133 ). Conversely, transgenic mice overexpressing MIF in alveolar epithelial cells had higher inflammation, viral load, and mortality ( 133 ). Finally, treatment of human lung epithelial cells with recombinant human MIF promoted the spread of IAV in vitro ( 133 ).…”

Section: Macrophage Migration Inhibitory Factor (Mif)mentioning

confidence: 90%

The Role of MIF and IL-10 as Molecular Yin-Yang in the Modulation of the Host Immune Microenvironment During Infections: African Trypanosome Infections as a Paradigm

et al. 2022

View full text Add to dashboard Cite

African trypanosomes are extracellular flagellated unicellular protozoan parasites transmitted by tsetse flies and causing Sleeping Sickness disease in humans and Nagana disease in cattle and other livestock. These diseases are usually characterized by the development of a fatal chronic inflammatory disease if left untreated. During African trypanosome infection and many other infectious diseases, the immune response is mediating a see-saw balance between effective/protective immunity and excessive infection-induced inflammation that can cause collateral tissue damage. African trypanosomes are known to trigger a strong type I pro-inflammatory response, which contributes to peak parasitaemia control, but this can culminate into the development of immunopathologies, such as anaemia and liver injury, if not tightly controlled. In this context, the macrophage migration inhibitory factor (MIF) and the interleukin-10 (IL-10) cytokines may operate as a molecular “Yin-Yang” in the modulation of the host immune microenvironment during African trypanosome infection, and possibly other infectious diseases. MIF is a pleiotropic pro-inflammatory cytokine and critical upstream mediator of immune and inflammatory responses, associated with exaggerated inflammation and immunopathology. For example, it plays a crucial role in the pro-inflammatory response against African trypanosomes and other pathogens, thereby promoting the development of immunopathologies. On the other hand, IL-10 is an anti-inflammatory cytokine, acting as a master regulator of inflammation during both African trypanosomiasis and other diseases. IL-10 is crucial to counteract the strong MIF-induced pro-inflammatory response, leading to pathology control. Hence, novel strategies capable of blocking MIF and/or promoting IL-10 receptor signaling pathways, could potentially be used as therapy to counteract immunopathology development during African trypanosome infection, as well as during other infectious conditions. Together, this review aims at summarizing the current knowledge on the opposite immunopathological molecular “Yin-Yang” switch roles of MIF and IL-10 in the modulation of the host immune microenvironment during infection, and more particularly during African trypanosomiasis as a paradigm.

show abstract

“…The established researches identified and elucidated two signal pathways of mitophagy: ubiquitin- (Ub-) dependent and Ub-independent (receptor-mediated mitophagy) [ 31 ]. Some study holds that MIF induces mitophagy via BNIP3-mediated pathway, an Ub-independent manner of mitophagy [ 32 ], while some other holds that MIF is the regulator of PINK1/Parkin-mediated mitophagy, the most well-defined Ub-mediated pathway of mitophagy [ 33 ]. The results of our prior and current studies elucidated that overload compression-associated mitophagy was related to the PINK1/Parkin-mediated macroautophagy [ 5 ].…”

Section: Discussionmentioning

confidence: 99%

Deficiency of MIF Accentuates Overloaded Compression‐Induced Nucleus Pulposus Cell Oxidative Damage via Depressing Mitophagy

Wang

et al. 2021

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Established studies proved that mechanical compression loading had multiple effects on the biological behavior of the intervertebral disc (IVD). However, the regulating mechanism involved in this process remains unclear. The current study is aimed at exploring the potential bioregulators and signaling pathways involved in the compression-associated biological changes of nucleus pulposus (NP) cells. Tandem mass tag- (TMT-) based quantitative proteomics was exerted to analyze the differentially expressed proteins (DEPs) and signal pathways among the different groups of NP cells cultured under noncompression, low-compression (LC), and high-compression (HC) loading. Eight potential protective bioregulators for the NP cell survival under different compression loading were predicted by the proteomics, among which macrophage migration inhibitory factor (MIF) and oxidative stress-related pathways were selected for further evaluation, due to its similar function in regulating the fate of the cartilage endplate- (CEP-) derived cells. We found that deficiency of MIF accentuates the accumulation of ROS, mitochondrial dysfunction, and senescence of NP cells under overloaded mechanical compression. The potential molecular mechanism involved in this process is related to the mitophagy regulating role of MIF. Our findings provide a better understanding of the regulatory role of mechanical compression on the cellular fate commitment and matrix metabolism of NP, and the potential strategies for treating disc degenerative diseases via using MIF-regulating agents.

show abstract

Macrophage migration inhibitory factor enhances influenza-associated mortality in mice

Abstract: Conflict of interest: RB is a coinventor on patents describing the therapeutic utility of anti-MIF (US9139877B2) and MIF antagonists (US9221903B2) and has received royalty payments in the past.

Cited by 18 publications

References 46 publications

Does Macrophage Migration Inhibitory Factor predict the prognosis of COVID-19 disease?

Does Macrophage Migration Inhibitory Factor predict the prognosis of COVID-19 disease?

The Role of MIF and IL-10 as Molecular Yin-Yang in the Modulation of the Host Immune Microenvironment During Infections: African Trypanosome Infections as a Paradigm

Deficiency of MIF Accentuates Overloaded Compression‐Induced Nucleus Pulposus Cell Oxidative Damage via Depressing Mitophagy

Contact Info

Product

Resources

About