Promising Therapeutic Effects of Embryonic Stem Cells-Origin Mesenchymal Stem Cells in Experimental Pulmonary Fibrosis Models: Immunomodulatory and Anti-Apoptotic Mechanisms.

Interstitial lung disease (ILD) involves persistent inflammation and fibrosis, leading to respiratory failure and even death. Adult tissue-derived mesenchymal stem cells (MSCs) show potential in ILD therapeutics but obtaining an adequate quantity of cells for drug application is difficult. Daewoong Pharmaceutical's MSCs (DW-MSCs) derived from embryonic stem cells sustain a high proliferative capacity following long-term culture and expansion.

Butyrate Improves Skin/Lung Fibrosis and Intestinal Dysbiosis in Bleomycin-Induced Mouse Models.

Systemic sclerosis (SSc) is an autoimmune disorder characterized by fibrosis of the skin and internal organs. Despite several studies on SSc treatments, effective treatments for SSc are still lacking. Since evidence suggests an association between intestinal microbiota and SSc, we focused on butyrate, which has beneficial effects in autoimmune diseases as a bacterial metabolite.

Resveratrol regulates naïve CD 8+ T-cell proliferation by upregulating IFN-γ-induced tryptophanyl-tRNA synthetase expression.

We found that resveratrol enhances interferon (IFN)-γ-induced tryptophanyl-tRNA-synthetase (TTS) expression in bone marrow- derived dendritic cells (BMDCs). Resveratrol-induced TTS expression is associated with glycogen synthase kinase-3β (GSK-3β) activity. In addition, we found that resveratrol regulates naïve CD8+ T-cell polarization by modulating GSK-3β activity in IFN-γ-stimulated BMDCs, and that resveratol induces upregulation of TTS in CD8+ T-cells in the in vivo tumor environment.

Resveratrol suppresses tumor progression via the regulation of indoleamine 2,3-dioxygenase.

This study showed the potential of resveratrol to inhibit the expression and activity of interferon-γ (IFN-γ)-induced indoleamine 2,3-dioxygenase (IDO) in bone marrow-derived dendritic cells (BMDCs). The mechanism of suppression was associated with the activity of Janus kinase/signal transducers and activators of transcription (JAK/STAT) and protein kinase Cδ (PKCδ). In addition, resveratrol-mediated IDO suppression in IFN-γ-stimulated BMDCs appears to play a pivotal role in anti-tumor activity through the regulation of CD8(+) T cell polarization and cytotoxic T lymphocyte (CTL) activity.

A possible usage of a CDK4 inhibitor for breast cancer stem cell-targeted therapy.

Cancer stem cells (CSCs) are one of the main reasons behind cancer recurrence due to their resistance to conventional anti-cancer therapies. Thus, many efforts are being devoted to developing CSC-targeted therapies to overcome the resistance of CSCs to conventional anti-cancer therapies and decrease cancer recurrence. Differentiation therapy is one potential approach to achieve CSC-targeted therapies.

Effect of low dose radiation on differentiation of bone marrow cells into dendritic cells.

Low dose radiation has been shown to be beneficial to living organisms using several biological systems, including immune and hematopoietic systems. Chronic low dose radiation was shown to stimulate immune systems, resulting in controlling the proliferation of cancer cells, maintain immune balance and induce hematopoietic hormesis. Since dendritic cells are differentiated from bone marrow cells and are key players in maintaining the balance between immune activation and tolerance, it may be important to further characterize whether low dose radiation can influence the capacity of bone marrow cells to differentiate into dendritic cells.

Outer membrane protein a of Salmonella enterica serovar Typhimurium activates dendritic cells and enhances Th1 polarization.

Background: Typhoid, which is caused by Salmonella enterica serovar Typhimurium, remains a major health concern worldwide. Multidrug-resistant strains of Salmonella have emerged which exhibit increased survivability and virulence, thus leading to increased morbidity. However, little is known about the protective immune response against this microorganism.

Induction of indoleamine 2,3-dioxygenase expression via heme oxygenase-1-dependant pathway during murine dendritic cell maturation.

Heme oxygenase (HO)-1 is expressed in a variety of conditions involved in the regulation of immune responses. In this study, we examined the role of HO-1 in dendritic cell (DC) maturation and expression of indoleamine 2,3-dioxygenase (IDO), a key enzyme that catalyzes the initial, rate-limiting step in tryptophan degradation. IDO deficiency led to diminished phenotypic and functional maturation of DCs in vitro and in vivo.

COX-2 and PGE2 signaling is essential for the regulation of IDO expression by curcumin in murine bone marrow-derived dendritic cells.

Indoleamine 2,3-dioxygenase (IDO), a key enzyme that catalyzes the initial, rate-limiting step in tryptophan degradation, is expressed in dendritic cells (DCs) which are stimulated by lipopolysaccharide (LPS) or interferons. In this study we show that curcumin inhibits IDO expression in vitro and in vivo in DCs, leading to the suppression of LPS-induced DC maturation. The effect of curcumin relative to LPS is not limited to the above, as it also enhances LPS-induced expression of cyclooxygenase (COX)-2 and production of prostaglandin E2 (PGE2).

Oncostatin M induces dendritic cell maturation and Th1 polarization.

Oncostatin M (OSM) is a pleiotropic cytokine and a member of the gp130/IL-6 cytokine family that has been found to be involved in both pro- and anti-inflammatory responses in cell-mediated immunity. Maturation of dendritic cells (DCs) is crucial for initiation of primary immune responses and is regulated by several stimuli. In this study, the role of OSM in the phenotypic and functional maturation of DCs was evaluated in vitro.

The novel role of platelet-activating factor in protecting mice against lipopolysaccharide-induced endotoxic shock.

Background: Platelet-activating factor (PAF) has been long believed to be associated with many pathophysiological processes during septic shock. Here we present novel activities for PAF in protecting mice against LPS-mediated endotoxic shock.

Principal Findings: In vivo PAF treatment immediately after LPS challenge markedly improved the survival rate against mortality from endotoxic shock.

Curcumin suppresses the induction of indoleamine 2,3-dioxygenase by blocking the Janus-activated kinase-protein kinase Cdelta-STAT1 signaling pathway in interferon-gamma-stimulated murine dendritic cells.

Indoleamine 2,3-dioxygenase (IDO) catalyzes the initial and rate-limiting step in the degradation of tryptophan and is strongly induced in interferon-gamma (IFNgamma)-stimulated dendritic cells (DCs). IDO has recently been established as a key enzyme in T-cell suppression-mediated immune tolerance to tumors. STAT1 phosphorylation appears to play an important role in the control of IDO expression by IFNgamma, but the precise regulatory mechanism remains obscure.

Quercetin regulates Th1/Th2 balance in a murine model of asthma.

Quercetin is found to be the most active of the flavonoids in studies and many medicinal plants owe much of their activity to their high Quercetin content. Quercetin has demonstrated significant anti-inflammatory activity because of direct inhibition of several initial processes of inflammation. However, its anti-allergic effect in the Th1/Th2 immune response was poorly understood.