MRP8 promotes Th17 differentiation via upregulation of IL-6 production by fibroblast-like synoviocytes in rheumatoid arthritis.
Abstract
Myeloid-related protein (MRP)8/MRP14 is an endogenous Toll-like receptor 4 (TLR4) ligand and is abundant in synovial fluid (SF) of rheumatoid arthritis (RA) patients. Belonging to damage-associated molecular patterns, it amplifies proinflammatory mediators and facilitates a wide range of inflammatory and autoimmune diseases. Interleukin (IL)-17-producing T-helper (Th)17 cells have a crucial role in RA pathogenesis, and IL-6 is the key factor promoting Th17 differentiation. We investigated whether the level of MRP8/MRP14 is positively associated with IL-6 and IL-17 levels in RA SF and found that MR...
Source: exp Mol Med - May 23, 2013 Category: Molecular Biology Authors: Lee DG, Woo JW, Kwok SK, Cho ML, Park SH Tags: Exp Mol Med Source Type: research
Pitt-Hopkins Syndrome: intellectual disability due to loss of TCF4-regulated gene transcription.
Abstract
TCF4 (transcription factor 4; E2-2, ITF2) is a transcription factor that when haplo-insufficient causes Pitt-Hopkins Syndrome (PTHS), an autism-spectrum disorder that is associated with pervasive developmental delay and severe intellectual disability. The TCF4 gene is also a risk factor with highly significant linkage to schizophrenia, presumably via overexpression of the TCF4 gene product in the central nervous system. This review will present an overview of the clinical manifestations of PTHS and relate those clinical attributes to the underlying molecular genetics of TCF4. In order to provide a...
Source: exp Mol Med - May 23, 2013 Category: Molecular Biology Authors: Sweatt JD Tags: Exp Mol Med Source Type: research
Autophagic failure promotes the exocytosis and intercellular transfer of α-synuclein.
Abstract
The accumulation of abnormal protein aggregates is a major characteristic of many neurodegenerative disorders, including Parkinson's disease (PD). The intracytoplasmic deposition of α-synuclein aggregates and Lewy bodies, often found in PD and other α-synucleinopathies, is thought to be linked to inefficient cellular clearance mechanisms, such as the proteasome and autophagy/lysosome pathways. The accumulation of α-synuclein aggregates in neuronal cytoplasm causes numerous autonomous changes in neurons. However, it can also affect the neighboring cells through transcellular transmission of the ...
Source: exp Mol Med - May 23, 2013 Category: Molecular Biology Authors: Lee HJ, Cho ED, Lee KW, Kim JH, Cho SG, Lee SJ Tags: Exp Mol Med Source Type: research
Inhibition of Janus activated kinase-3 protects against myocardial ischemia and reperfusion injury in mice.
Abstract
Recent studies have documented that Janus-activated kinase (JAK)-signal transducer and activator of transcription (STAT) pathway can modulate the apoptotic program in a myocardial ischemia/reperfusion (I/R) model. To date, however, limited studies have examined the role of JAK3 on myocardial I/R injury. Here, we investigated the potential effects of pharmacological JAK3 inhibition with JANEX-1 in a myocardial I/R model. Mice were subjected to 45 min of ischemia followed by varying periods of reperfusion. JANEX-1 was injected 1 h before ischemia by intraperitoneal injection. Treatment with JANE...
Source: exp Mol Med - May 23, 2013 Category: Molecular Biology Authors: Oh YB, Ahn M, Lee SM, Koh HW, Lee SH, Kim SH, Park BH Tags: Exp Mol Med Source Type: research
Retrovirus-mediated transduction of a cytosine deaminase gene preserves the stemness of mesenchymal stem cells.
Abstract
Human mesenchymal stem cells (MSCs) have emerged as attractive cellular vehicles to deliver therapeutic genes for ex-vivo therapy of diverse diseases; this is, in part, because they have the capability to migrate into tumor or lesion sites. Previously, we showed that MSCs could be utilized to deliver a bacterial cytosine deaminase (CD) suicide gene to brain tumors. Here we assessed whether transduction with a retroviral vector encoding CD gene altered the stem cell property of MS...
Source: exp Mol Med - February 25, 2013 Category: Molecular Biology Authors: Sung Park J, Chang DY, Kim JH, Hwa Jung J, Park J, Kim SH, Lee YD, Kim SS, Suh-Kim H Tags: Exp Mol Med Source Type: research
Negative regulatory approaches to the attenuation of Toll-like receptor signaling.
Abstract
Toll-like receptors (TLRs) are pivotal components of the innate immune response, which is responsible for eradicating invading microorganisms through the induction of inflammatory molecules. These receptors are also involved in responding to harmful endogenous molecules and have crucial roles in the activation of the innate immune system and shaping the adaptive immune response. However, TLR signaling pathways must be tightly regulated because undue TLR stimulation may disrupt the fine balance between pro- and anti-inflammatory responses. Such disruptions may harm the host through the development ...
Source: exp Mol Med - February 25, 2013 Category: Molecular Biology Authors: Anwar MA, Basith S, Choi S Tags: Exp Mol Med Source Type: research
Identification of a genetic locus on chromosome 4q34-35 for type 2 diabetes with overweight.
Abstract
The incidence of type 2 diabetes is rising rapidly because of an increase in the incidence of being overweight and obesity. Identification of genetic determinants for complex diseases, such as type 2 diabetes, may provide insight into disease pathogenesis. The aim of the study was to investigate the shared genetic factors that predispose individuals to being overweight and developing type 2 diabetes. We conducted genome-wide linkage analyses for type 2 diabetes in 386 affected individuals (269 sibpairs) from 171 Korean families and association analyses with single-nucleotide polymorphisms of candi...
Source: exp Mol Med - February 16, 2013 Category: Molecular Biology Authors: Park MH, Kwak SH, Kim KJ, Go MJ, Lee HJ, Kim KS, Hwang JY, Kimm K, Cho YM, Kyu Lee H, Park KS, Lee JY Tags: Exp Mol Med Source Type: research
Rhamnogalacturonan II is a Toll-like receptor 4 agonist that inhibits tumor growth by activating dendritic cell-mediated CD8(+) T cells.
Abstract
We evaluated the effectiveness of rhamnogalacturonan II (RG-II)-stimulated bone marrow-derived dendritic cells (BMDCs) vaccination on the induction of antitumor immunity in a mouse lymphoma model using EG7-lymphoma cells expressing ovalbumin (OVA). BMDCs treated with RG-II had an activated phenotype. RG-II induced interleukin (IL)-12, IL-1β, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) production during dendritic cell (DC) maturation. BMDCs stimulated with RG-II facilitate the proliferation of CD8(+) T cells. Using BMDCs from the mice deficient in Toll-like receptors (TLRs), we re...
Source: exp Mol Med - February 16, 2013 Category: Molecular Biology Authors: Park SN, Tae Noh K, Jeong YI, Duk Jung I, Kyu Kang H, Sun Cha G, Jung Lee S, Keun Seo J, Hwan Kang D, Hwang TH, Kyung Lee E, Kwon B, Park YM Tags: Exp Mol Med Source Type: research
Activated protein C differentially regulates both viability and differentiation of osteoblasts mediated by bisphosphonates.
We examined the effect of APC on viability and differentiation of the osteoblastic line, MG63, in the presence and absence of bisphosphonates (BPs). Osteoblasts were cultured and treated for 24 or 48 h with Alendronate (Aln), Zoledronate (Zol) or Pamidronate (Pam) at concentrations ranging from 10(-4) to 10(-6) M. Cell differentiation was measured using type 1 collagen production, Alizarin red staining and alkaline phosphatase activity, whereas cell viability was assessed using MTT and crystal violet assays. All three BPs induced MG63 cell death in a dose- and time-dependent manner. Pam- and Zol-related cell death was ...
Source: exp Mol Med - February 16, 2013 Category: Molecular Biology Authors: Lee YJ, Jeong JK, Seol JW, Xue M, Jackson C, Park SY Tags: Exp Mol Med Source Type: research
Another leap for EMM into a new era.
PMID: 23306699 [PubMed - in process] (Source: exp Mol Med)
Source: exp Mol Med - January 28, 2013 Category: Molecular Biology Authors: Jue DM Tags: Exp Mol Med Source Type: research
The potential use of mesenchymal stem cells in hematopoietic stem cell transplantation.
Abstract
In the last 10 years, mesenchymal stem cells (MSCs) have emerged as a therapeutic approach to regenerative medicine, cancer, autoimmune diseases, and many more due to their potential to differentiate into various tissues, to repair damaged tissues and organs, and also for their immunomodulatory properties. Findings in vitro and in vivo have demonstrated immune regulatory function of MSCs and have facilitated their application in clinical trials, such as those of autoimmune diseases and chronic inflammatory diseases. There has been an increasing interest in the role of MSCs in allogeneic hematopoie...
Source: exp Mol Med - January 28, 2013 Category: Molecular Biology Authors: Kim EJ, Kim N, Cho SG Tags: Exp Mol Med Source Type: research
ANT2 suppression by shRNA restores miR-636 expression, thereby downregulating Ras and inhibiting tumorigenesis of hepatocellular carcinoma.
Abstract
MicroRNAs (miRNAs) participate in diverse biological functions and carcinogenesis by inhibiting specific gene expression. We previously reported that suppression of adenine nucleotide translocase 2 (ANT2) by using the short hairpin RNA (shRNA) approach has an antitumor effect in several cancer cells. We here examined the influence of ANT2 on expression of miRNAs in hepatocellular carcinoma (HCC) to further elucidate the tumor-suppressive mechanism of ANT2 shRNA. We first carried out screening for miRNAs, whose expression is regulated by ANT2 suppression in the Hep3B HCC cell line using miRNA micro...
Source: exp Mol Med - January 28, 2013 Category: Molecular Biology Authors: Jang JY, Lee YS, Jeon YK, Lee K, Jang JJ, Kim CW Tags: Exp Mol Med Source Type: research
B-cell-activating factor is a regulator of adipokines and a possible mediator between adipocytes and macrophages.
We examined adipokine expression in 3T3-L1 adipocytes treated with 10 ng ml(-1) BAFF. We also examined inflammatory molecule expression in RAW 264.7 macrophages treated with 10 or 100 ng ml(-1) BAFF. We examined BAFF expression in the coculture of 3T3-L1 adipocytes and RAW 264.7 macrophages, as well as in white adipose tissue (WAT) of diet-induced obese (DIO) mice. We found that BAFF decreases leptin and adiponectin expression, but increases the expression of proinflammatory adipokines monocyte chemotactic protein-1, interleukin-6 (IL-6), cyclooxygenase-2 (COX-2) and haptoglobin. Coculturing the two cell types resu...
Source: exp Mol Med - January 28, 2013 Category: Molecular Biology Authors: Kim MY, Kim DH, Do MS Tags: Exp Mol Med Source Type: research
Acetyl salicylic acid inhibits Th17 airway inflammation via blockade of IL-6 and IL-17 positive feedback.
Abstract
T-helper (Th)17 cell responses are important for the development of neutrophilic inflammatory disease. Recently, we found that acetyl salicylic acid (ASA) inhibited Th17 airway inflammation in an asthma mouse model induced by sensitization with lipopolysaccharide (LPS)-containing allergens. To investigate the mechanism(s) of the inhibitory effect of ASA on the development of Th17 airway inflammation, a neutrophilic asthma mouse model was generated by intranasal sensitization with LPS plus ovalbumin (OVA) and then challenged with OVA alone. Immunologic parameters and airway inflammation were evalua...
Source: exp Mol Med - January 28, 2013 Category: Molecular Biology Authors: Moon HG, Kang CS, Choi JP, Choi DS, Choi HI, Choi YW, Jeon SG, Yoo JY, Jang MH, Gho YS, Kim YK Tags: Exp Mol Med Source Type: research
Regulation of osteogenic differentiation of human adipose-derived stem cells by controlling electromagnetic field conditions.
This study provides a framework for future work on controlling stem cell differentiation.
PMID: 23306704 [PubMed - in process] (Source: exp Mol Med)
Source: exp Mol Med - January 28, 2013 Category: Molecular Biology Authors: Kang KS, Hong JM, Kang JA, Rhie JW, Jeong YH, Cho DW Tags: Exp Mol Med Source Type: research
