Cytokine-Induced iNOS in A549 Alveolar Epithelial Cells: A Potential Role in COVID-19 Lung Pathology.

Background: In COVID-19, an uncontrolled inflammatory response might worsen lung damage, leading to acute respiratory distress syndrome (ARDS). Recent evidence points to the induction of inducible nitric oxide synthase (/iNOS) as a component of inflammatory response since is upregulated in critical COVID-19 patients. Here, we explore the mechanisms underlying the modulation of iNOS expression in human alveolar cells.

Growth Arrest of Alveolar Cells in Response to Cytokines from Spike S1-Activated Macrophages: Role of IFN-γ.

Acute respiratory distress syndrome (ARDS) is characterized by severe hypoxemia and high-permeability pulmonary edema. A hallmark of the disease is the presence of lung inflammation with features of diffuse alveolar damage. The molecular pathogenetic mechanisms of COVID-19-associated ARDS (CARDS), secondary to SARS-CoV-2 infection, are still not fully understood.

The JAK1/2 Inhibitor Baricitinib Mitigates the Spike-Induced Inflammatory Response of Immune and Endothelial Cells In Vitro.

The purpose of this study was to examine the effect of the JAK-STAT inhibitor baricitinib on the inflammatory response of human monocyte-derived macrophages (MDM) and endothelial cells upon exposure to the spike S1 protein from SARS-CoV-2. The effect of the drug has been evaluated on the release of cytokines and chemokines from spike-treated MDM, as well as on the activation of endothelial cells (HUVECs) after exposure to conditioned medium collected from spike-activated MDM. Results obtained indicate that, in MDM, baricitinib prevents the S1-dependent phosphorylation of STAT1 and STAT3, along with the induction of IP-10- and MCP-1 secretion; the release of IL-6 and TNFα is also reduced, while all other mediators tested (IL-1β, IL-8, RANTES, MIP-1α and MIP-1β) are not modified.

Immune tolerance induction by nonmyeloablative haploidentical HSCT combining T-cell depletion and posttransplant cyclophosphamide.

The establishment of safe approaches to attain durable donor-type chimerism and immune tolerance toward donor antigens represents a major challenge in transplantation biology. Haploidentical hematopoietic stem cell transplantation (HSCT) is currently used for cancer therapy either as a T-cell-depleted megadose HSCT following myeloablative conditioning or with T-cell-replete HSCT following nonmyeloablative conditioning (NMAC) and high-dose posttransplant cyclophosphamide (PTCY). The latter approach suffers from a significant rate of chronic graft-versus-host disease (GVHD), despite prolonged immunosuppression.

Increased production of soluble HLA-G molecules in stimulated peripheral blood mononuclear cells following extracorporeal photopheresis: is it a mechanism involved in the therapeutic effect of the procedure?

We hypothesized that the effects of extracorporeal photopheresis (ECP) are mediated by induction of immunosuppressive cytokines like IL-10, which enhances synthesis of HLA-G molecules. HLA-G products are expressed by CD14+ peripheral blood mononuclear cells (PBMC) and play an important role in inhibition of cell mediated immunity. ECP induces apoptosis in lymphocytes but not in CD14+ cells.

In vitro removal of therapeutic drugs with a novel adsorbent system.

Background/aims: Substances in the middle molecular weight range have been shown to play a significant pathogenetic role in as diverse disorders as end-stage renal disease and multiple organ failure. To overcome the limitations in the amount removed by hemofilters, new sorbents with a high biocompatibility are actively being developed. Furthermore, biocompatible sorbents by their nonspecific adsorptive behavior could have great impact on detoxification treatment in exogenous intoxications.