Macrophage migration inhibitory factor polymorphisms are a potential susceptibility marker in systemic sclerosis from southern Mexican population: association with MIF mRNA expression and cytokine profile

Baños‐Hernández, Christian Johana; Navarro‐Zarza, José Eduardo; Bucala, Richard; Hernández‐Bello, Jorge; Parra‐Rojas, Isela; Ramírez‐Dueñas, Maria Guadalupe; García‐Arellano, Samuel; Hernández-Palma, Luis Alexis; Machado-Sulbaran, Andrea Carolina; Muñoz‐Valle, José Francisco

doi:10.1007/s10067-019-04459-8

Cited by 20 publications

(19 citation statements)

References 56 publications

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“…In response to pathogen infection, inflammatory reactions are activated through recognizing pathogens by pattern recognition receptors (PPRs) in macrophages, such as toll‐like receptors (TLRs). Disordered inflammatory response is known to be one of the most important causes of autoimmune diseases, such as inflammatory bowel diseases, 1,2 systemic sclerosis, 3 polymyositis, 4 and diabetes 5 . Thus, defining the mechanisms of inflammation regulation is then considered of great importance.…”

Section: Introductionmentioning

confidence: 99%

TRAF3 promotes ROS production and pyroptosis by targeting ULK1 ubiquitination in macrophages

et al. 2020

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oxygen species; TLR, toll-like receptor; TRAF3, tumor necrosis factor receptorassociated factor 3; ULK1, Unc-51 like autophagy activating kinase 1. AbstractDisrupted mitochondrial function and reactive oxygen species (ROS) generation cause cellular damage and oxidative stress-induced macrophage inflammatory cell death. It remains unclear how mitochondrial dysfunction relates to inflammasome activation and pyroptotic cell death. In this study, we demonstrated that tumor necrosis factor receptor-associated factor 3 (TRAF3) regulates mitochondrial ROS production and promotes TLR agonist LPS plus nigericin (LPS/Ng)-induced inflammasome and pyroptosis in mouse primary macrophages and human monocyte THP-1 cells. Co-IP assays confirmed that TRAF3 forms a complex with TRAF2 and cIAP1 and mediates ubiquitin and degradation of Unc-51 like autophagy activating kinase 1 (ULK1). Moreover, knockdown of ULK1 in THP-1 cells significantly promoted LPS/Ng-induced inflammasome by activating caspase 1 and mature IL-1β. Apoptosis inducing factor (AIF) translocation from mitochondrial to nuclear was observed in ULK1-deficient THP-1 cells under LPS/Ng stimulation, which mediates LPS/Ng-induced cell death in ULK1 deficient macrophages. In conclusion, this study identified a novel role of TRAF3 in regulation of ULK1 ubiquitination and inflammasome signaling and provided molecular mechanisms by which ubiquitination of ULK1 controls mitochondrial ROS production, inflammasome activity, and AIF-dependent pyroptosis. K E Y W O R D S cell death, inflammasome, macrophages, mitochondrial, reactive oxygen species | 7145 SHEN Et al.

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Section: Introductionmentioning

confidence: 99%

TRAF3 promotes ROS production and pyroptosis by targeting ULK1 ubiquitination in macrophages

et al. 2020

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“…Therefore, we assessed the distribution of two predominant MIF promoter polymorphisms associated with MIF expression alterations in our cohort: the single nucleotide polymorphism (SNP) rs755622 and rs5844572 -a microsatellite marker of the tetra nucleotide motive "CATT". Less frequent genotypes (C/C; CATT7/X) of both polymorphisms show increased basal transcriptional activity of the MIF promoter [12,24,25]. In our cohort, the MIF promoter variant SNP -173C correlated with sCD74 concentrations as patients with C/C genotype had significantly decreased sCD74 serum concentrations (Suppl.…”

Section: The Investigated Mif Promoter Variants G/c -173 and (Catt) 5mentioning

confidence: 57%

“…Among others, the transcriptional activity of MIF is influenced by promoter polymorphisms: rs755622 represents a single nucleotide polymorphism (SNP) whereas rs5844572 is a microsatellite marker of the tetra nucleotide motive "CATT" with alleles ranging from five to eight repeats (CATT5, CATT6, CATT7 or J o u r n a l P r e -p r o o f CATT8). Less frequent genotypes (C/C; CATT7/X) of both polymorphisms show increased basal transcriptional activity of the MIF promoter [12,24,25].…”

Section: Introductionmentioning

confidence: 97%

Balance between macrophage migration inhibitory factor and sCD74 predicts outcome in patients with acute decompensation of cirrhosis

et al. 2021

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Background & Aims Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine and an important regulator of innate immune responses. We hypothesised that serum concentrations of MIF are associated with disease severity and outcome in patients with decompensated cirrhosis and acute-on-chronic liver failure (ACLF). Methods Circulating concentrations of MIF and its soluble receptor CD74 (sCD74) were determined in sera from 292 patients with acute decompensation of cirrhosis defined as new onset or worsening of ascites requiring hospitalisation. Of those, 78 (27%) had ACLF. Short-term mortality was assessed 90 days after inclusion. Results Although serum concentrations of MIF and sCD74 did not correlate with liver function parameters or ACLF, higher MIF (optimum cut-off >2.3 ng/ml) and lower concentrations of sCD74 (optimum cut-off <66.5 ng/ml) both indicated poorer 90-day transplant-free survival in univariate analyses (unadjusted hazard ratio [HR] 2.01 [1.26–3.22]; p = 0.004 for MIF; HR 0.59 [0.38–0.92]; p = 0.02 for sCD74) and after adjustment in multivariable models. Higher MIF concentrations correlated with surrogates of systemic inflammation (white blood cells, p = 0.005; C-reactive protein, p = 0.05) and were independent of genetic MIF promoter polymorphisms. Assessment of MIF plasma concentrations in portal venous blood and matched blood samples from the right atrium in a second cohort of patients undergoing transjugular intrahepatic portosystemic shunt insertion revealed a transhepatic MIF gradient with higher concentrations in the right atrial blood. Conclusions Serum concentrations of MIF and its soluble receptor CD74 predict 90-day transplant-free survival in patients with acute decompensation of cirrhosis. This effect was independent of liver function and genetic predispositions, but rather reflected systemic inflammation. Therefore, MIF and sCD74 represent promising prognostic markers beyond classical scoring systems in patients at risk of ACLF. Lay summary Inflammatory processes contribute to the increased risk of death in patients with cirrhosis and ascites. We show that patients with high serum levels of the inflammatory cytokine macrophage migration inhibitory factor (MIF) alongside low levels of its binding receptor sCD74 in blood indicate an increased mortality risk in patients with ascites. The cirrhotic liver is a relevant source of elevated circulating MIF levels.

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“…High level of the myeloid cell chemo-attractant CCL2 has been found in the skin of SSc patients with the inflammatory subset and both CCL2 mRNA and CCL2 serum levels decreased during treatment with MMF. Finally, the same study confirmed the role of macrophages [25] and myeloid dendritic cells (mDC) in SSc pathogenesis, as their level seems to decrease during MMF treatment and correlate with inflammatory NES [13]. The use of belimumab and MMF for the treatment of SSc also showed similar results [26], although, authors did not show significant differences in mRSS improvement between patients treated with belimumab compared with placebo.…”

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confidence: 55%

Recent advances steer the future of systemic sclerosis toward precision medicine

et al. 2019

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Macrophage migration inhibitory factor polymorphisms are a potential susceptibility marker in systemic sclerosis from southern Mexican population: association with MIF mRNA expression and cytokine profile

Cited by 20 publications

References 56 publications

TRAF3 promotes ROS production and pyroptosis by targeting ULK1 ubiquitination in macrophages

TRAF3 promotes ROS production and pyroptosis by targeting ULK1 ubiquitination in macrophages

Balance between macrophage migration inhibitory factor and sCD74 predicts outcome in patients with acute decompensation of cirrhosis

Recent advances steer the future of systemic sclerosis toward precision medicine

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