Upregulation of IL-1 Receptor Antagonist in a Mouse Model of Migraine

Lombardo, Salvo Danilo; Mazzon, Emanuela; Basile, Maria Sofia; Cavalli, Eugenio; Bramantı, Placido; Nania, Riccardo; Fagone, Paolo; Nicoletti, Ferdinando; Petralia, Maria Cristina

doi:10.3390/brainsci9070172

Cited by 29 publications

(21 citation statements)

References 73 publications

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“…We also studied the possible diagnostic and prognostic value of TSPAN32 expression in PBMC of MS patients, on the course of the disease. The use of whole-genome expression databases has been largely exploited [25][26][27][28] for the characterization of pathogenic pathways and to identify therapeutic targets for a variety of disorders, including immunoinflammatory and autoimmune diseases [29][30][31][32][33][34][35][36], cancer [37][38][39], and has allowed dismantling pathogenetic pathways [40][41][42], along with the identification of novel tailored therapeutic targets [43][44][45][46].…”

Section: Discussionmentioning

confidence: 99%

Impaired Expression of Tetraspanin 32 (TSPAN32) in Memory T Cells of Patients with Multiple Sclerosis

et al. 2020

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Tetraspanins are a conserved family of proteins involved in a number of biological processes. We have previously shown that Tetraspanin-32 (TSPAN32) is significantly downregulated upon activation of T helper cells via anti-CD3/CD28 stimulation. On the other hand, TSPAN32 is marginally modulated in activated Treg cells. A role for TSPAN32 in controlling the development of autoimmune responses is consistent with our observation that encephalitogenic T cells from myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) mice exhibit significantly lower levels of TSPAN32 as compared to naïve T cells. In the present study, by making use of ex vivo and in silico analysis, we aimed to better characterize the pathophysiological and diagnostic/prognostic role of TSPAN32 in T cell immunity and in multiple sclerosis (MS). We first show that TSPAN32 is significantly downregulated in memory T cells as compared to naïve T cells, and that it is further diminished upon ex vivo restimulation. Accordingly, following antigenic stimulation, myelin-specific memory T cells from MS patients showed significantly lower expression of TSPAN32 as compared to memory T cells from healthy donors (HD). The expression levels of TSPAN32 was significantly downregulated in peripheral blood mononuclear cells (PBMCs) from drug-naïve MS patients as compared to HD, irrespective of the disease state. Finally, when comparing patients undergoing early relapses in comparison to patients with longer stable disease, moderate but significantly lower levels of TSPAN32 expression were observed in PBMCs from the former group. Our data suggest a role for TSPAN32 in the immune responses underlying the pathophysiology of MS and represent a proof-of-concept for additional studies aiming at dissecting the eventual contribution of TSPAN32 in other autoimmune diseases and its possible use of TSPAN32 as a diagnostic factor and therapeutic target.

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Section: Discussionmentioning

confidence: 99%

Impaired Expression of Tetraspanin 32 (TSPAN32) in Memory T Cells of Patients with Multiple Sclerosis

et al. 2020

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“…In addition, we also evaluated the transcriptomic analysis of MIF, DDT and their receptors in the brains of a mouse model of alcoholism. This analysis was carried out by DNA microarray analysis that represents a useful in silico toll for the better understanding of pathogenic pathways and the possible prediction of new diagnostic therapeutic approaches in several clinical settings, including immunoinflammatory and autoimmune diseases and fibrotic diseases (45,46,(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59). Our analysis first demonstrated that no differences in the expression of MIF, DDT and their receptors can be found in brains of both rodent models of AUD and patients with this condition.…”

Section: Discussionmentioning

confidence: 83%

Transcriptomic analysis reveals moderate modulation of macrophage migration inhibitory factor superfamily genes in alcohol use disorders

et al. 2020

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Alcohol use disorder (AUD) is a primary, chronic and relapsing disease of brain reward, motivation and memory, which is associated with several comorbidities, including major depression and post-traumatic stress disorder. It has been revealed that Ibudilast (IBUD), a dual inhibitor of phosphodiesterase-4 and-10 and of macrophage migration inhibitory factor (MIF), exerts beneficial effects on AUD in rodent models and human patients. Therefore, IBUD has attracted increasing interest, with research focusing on the elucidation of the pathogenic role of MIF and its homologue, D-dopachrome tautomerase (DDT), in the pathogenesis and maintenance of AUD. By using DNA microarray analysis, the current study performed a transcriptomic expression analysis of MIF, DDT and their co-receptors, including CD74, C-X-C chemokine receptor (CXCR)2, CXCR4 and CXCR7 in patients with AUD. The results revealed that the transcriptomic levels of MIF, DDT and their receptors were superimposable in the prefrontal cortex of rodents and patients with AUD and human patients. Furthermore, peripheral blood cells from heavy drinkers exhibited a moderate increase in MIF and DDT levels, both at the baseline and following exposure to alcohol-associated cues, based on individual situations that included alcohol-related stimuli resulting in subsequent alcohol use (buying alcohol and being at a bar, watching others drink alcohol). Considering the overlapping effects of MIF and DDT, the inverse Fisher's χ 2 test was performed on unadjusted P-values to evaluate the combined effect of MIF and DDT. The results revealed a significant increase in these cytokines in heavy drinkers compared with controls (moderate drinkers). To the best of our knowledge, the present study demonstrated for the first time that MIF and DDT expression was upregulated in the blood of patients with AUD. These results therefore warrant further study to evaluate the role of MIF and DDT in the development and maintenance of AUD, to evaluate their use as biomarkers to predict the psychotherapeutic and pharmacological response of patients with AUD and for use as therapeutic targets.

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“…To our knowledge, this is the first meta-analysis to be performed exclusively on studies performed on a specific brain region from SCZ subjects and controls, rather than on studies encompassing different Brodmann areas or brain anatomical structures. The use of whole-genome expression databases has been largely exploited by our group and others [37][38][39][40][41] for the characterization of pathogenic pathways and to identify therapeutic targets for a variety of disorders, such as autoimmune diseases [42][43][44][45][46][47][48][49][50], cancer [44,51,52], and has allowed researchers to characterize pathogenic pathways [53][54][55][56], and potential therapeutic targets [57][58][59][60][61].…”

Section: Discussionmentioning

confidence: 99%

Meta-Analysis of Transcriptomic Data of Dorsolateral Prefrontal Cortex and of Peripheral Blood Mononuclear Cells Identifies Altered Pathways in Schizophrenia

Petralia

Saraceno

Pennisi

et al. 2020

Genes

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Schizophrenia (SCZ) is a psychiatric disorder characterized by both positive and negative symptoms, including cognitive dysfunction, decline in motivation, delusion and hallucinations. Antipsychotic agents are currently the standard of care treatment for SCZ. However, only about one-third of SCZ patients respond to antipsychotic medications. In the current study, we have performed a meta-analysis of publicly available whole-genome expression datasets on Brodmann area 46 of the brain dorsolateral prefrontal cortex in order to prioritize potential pathways underlying SCZ pathology. Moreover, we have evaluated whether the differentially expressed genes in SCZ belong to specific subsets of cell types. Finally, a cross-tissue comparison at both the gene and functional level was performed by analyzing the transcriptomic pattern of peripheral blood mononuclear cells of SCZ patients. Our study identified a robust disease-specific set of dysfunctional biological pathways characterizing SCZ patients that could in the future be exploited as potential therapeutic targets.

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Upregulation of IL-1 Receptor Antagonist in a Mouse Model of Migraine

Cited by 29 publications

References 73 publications

Impaired Expression of Tetraspanin 32 (TSPAN32) in Memory T Cells of Patients with Multiple Sclerosis

Impaired Expression of Tetraspanin 32 (TSPAN32) in Memory T Cells of Patients with Multiple Sclerosis

Transcriptomic analysis reveals moderate modulation of macrophage migration inhibitory factor superfamily genes in alcohol use disorders

Meta-Analysis of Transcriptomic Data of Dorsolateral Prefrontal Cortex and of Peripheral Blood Mononuclear Cells Identifies Altered Pathways in Schizophrenia

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