Search results for "uno"

COVID-19: unravelling the clinical progression of nature’s virtually perfect biological weapon

2020

Coronavirus disease 2019 (COVID-19) pandemic has shocked the world and caused morbidity and mortality on an unprecedented level in the era of modern medicine. Evidence generated to-date on the virulence and pathogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suggests that COVID-19 may be considered a perfect storm, caused by a nature’s virtually perfect biological weapon. This conclusion is supported by an updated analysis of pathogenesis and clinical progression of this infectious disease. It is now readily apparent that COVID-19 is not a clear-cut disorder, but is instead a gradually evolving pathology, characterized by a series of stages sustained by different m…

Human molecular chaperones share with SARS-CoV-2 antigenic epitopes potentially capable of eliciting autoimmunity against endothelial cells: possible…

2020

Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), the cause of COVID-19 disease, has the potential to elicit autoimmunity because mimicry of human molecular chaperones by viral proteins. We compared viral proteins with human molecular chaperones, many of which are heat shock proteins, to determine if they share amino acid-sequence segments with immunogenic-antigenic potential, which can elicit cross-reactive antibodies and effector immune cells with the capacity to damage-destroy human cells by a mechanism of autoimmunity. We identified the chaperones that can putatively participate in molecular mimicry phenomena after SARS-CoV-2 infection, focusing on those for which endotheli…

Antibody-mediated blockade of JMJD6 interaction with collagen I exerts antifibrotic and antimetastatic activities

2017

JMJD6 is known to localize in the nucleus, exerting histone arginine demethylase and lysyl hydroxylase activities. A novel localization of JMJD6 in the extracellular matrix, resulting from its secretion as a soluble protein, was unveiled by a new anti-JMJD6 mAb called P4E11, which was developed to identify new targets in the stroma. Recombinant JMJD6 binds with collagen type I (Coll-I), and distinct JMJD6 peptides interfere with collagen fibrillogenesis, collagen-fibronectin interaction, and adhesion of human tumor cells to the collagen substrate. P4E11 and collagen binding to JMJD6 are mutually exclusive because the amino acid sequences of JMJD6 necessary for the interaction with Coll-I ar…

Notch and TLR signaling coordinate monocyte cell fate and inflammation

2020

AbstractConventional Ly6Chi monocytes have developmental plasticity for a spectrum of differentiated phagocytes. Here we show, using conditional deletion strategies in a mouse model of Toll-like receptor (TLR) 7-induced inflammation, that the spectrum of developmental cell fates of Ly6Chi monocytes, and the resultant inflammation, is coordinately regulated by TLR and Notch signaling. Cell-intrinsic Notch2 and TLR7-Myd88 pathways independently and synergistically promote Ly6Clo patrolling monocyte development from Ly6Chi monocytes under inflammatory conditions, while impairment in either signaling axis impairs Ly6Clo monocyte development. At the same time, TLR7 stimulation in the absence of …

Beyond protein-coding genes

2019

A long non-coding RNA called lnc-NR2F1 regulates several neuronal genes, including some involved in autism and intellectual disabilities.

The fibronectin synergy site re-enforces cell adhesion and mediates a crosstalk between integrin classes

2017

Fibronectin (FN), a major extracellular matrix component, enables integrin-mediated cell adhesion via binding of α5β1, αIIbβ3 and αv-class integrins to an RGD-motif. An additional linkage for α5 and αIIb is the synergy site located in close proximity to the RGD motif. We report that mice with a dysfunctional FN-synergy motif (Fn1syn/syn) suffer from surprisingly mild platelet adhesion and bleeding defects due to delayed thrombus formation after vessel injury. Additional loss of β3 integrins dramatically aggravates the bleedings and severely compromises smooth muscle cell coverage of the vasculature leading to embryonic lethality. Cell-based studies revealed that the synergy site is dispensa…

2016

AbstractDespite the high global prevalence of dry eye syndrome (DES), the fundamental processes underlying this pathology remain largely unexplored. Therefore, this study endeavoured to investigate in-depth the tear proteome of DES patients employing the mass spectrometry (MS)-based proteomic strategies. Eighty patients were recruited and subdivided into three major DES subgroups, which are the aqueous-deficient (DRYaq), evaporative (DRYlip) and a combination of the two (DRYaqlip), as well as healthy subjects (CTRL). Discovery proteomics strategy was employed to identify large number of significantly differentially expressed tear proteins in DRYlip vs. CTRL, DRYaq vs. CTRL and DRYaqlip vs. …

2016

Interleukin-1 (IL-1) plays a crucial role in numerous inflammatory diseases via action on its only known signaling IL-1 receptor type 1 (IL-1R1). To investigate the role of IL-1 signaling in selected cell types, we generated a new mouse strain in which exon 5 of the Il1r1 gene is flanked by loxP sites. Crossing of these mice with CD4-Cre transgenic mice resulted in IL-1R1 loss of function specifically in T cells. These mice, termed IL-1R1ΔT, displayed normal development under steady state conditions. Importantly, isolated CD4 positive T cells retained their capacity to differentiate toward Th1 or Th17 cell lineages in vitro, and strongly proliferated in cultures supplemented with either ant…

2016

Psoriasis is an autoimmune skin disease that is associated with aberrant activity of immune cells and keratinocytes. In mice, topical application of TLR7/8 agonist IMQ leads to a skin disorder resembling human psoriasis. Recently, it was shown that the IL-23/ IL-17 axis plays a deciding role in the pathogenesis of human psoriasis, as well as in the mouse model of IMQ-induced psoriasis-like skin disease. A consequence of IL-17A production in the skin includes increased expression and production of IL-6, resulting in the recruitment of neutrophils and other myelomonocytic cells to the site of inflammation. To further investigate and characterize the exact role of IL-6 signaling in myelomonocy…

2018

In this study we analysed the effects of prophylactic biolistic DNA vaccination with plasmids encoding the encephalitogenic protein myelin oligodendrocyte glycoprotein (MOG) on the severity of a subsequently MOGp35-55-induced EAE and on the underlying immune response. We compared the outcome of vaccination with MOG-encoding plasmids alone or in combination with vectors encoding the regulatory cytokines IL-10 and TGF-s1, respectively. MOG expression was restricted to skin dendritic cells (DCs) by the use of the DC-specific promoter of the fascin1 gene (pFscn-MOG). For comparison, the strong and ubiquitously active CMV promoter was employed (pCMV-MOG), which allows MOG expression in all trans…