The Fos-Related Antigen 1-JUNB/Activator Protein 1 Transcription Complex, a Downstream Target of Signal Transducer and Activator of Transcription 3, Induces T Helper 17 Differentiation and Promotes Experimental Autoimmune Arthritis.

Dysfunction of T helper 17 (Th17) cells leads to chronic inflammatory disorders. Signal transducer and activator of transcription 3 (STAT3) orchestrates the expression of proinflammatory cytokines and pathogenic cell differentiation from interleukin (IL)-17-producing Th17 cells. However, the pathways mediated by STAT3 signaling are not fully understood.

Csk Regulates Blood Pressure by Controlling the Synthetic Pathways of Aldosterone.

Background: Blood pressure is regulated by a network of diverse physiological pathways. The C-terminal Src kinase (CSK) locus (15q24) is associated with blood pressure in various ethnic groups. It was recently reported thatCskinsufficiency increases blood pressure through Src.

CFL-1, a novel F-box protein with leucine-rich repeat may interact with UNC-10 for the regulation of defecation and daumone response in .

Previously we reported that CFL-1, the single LRR-type F-box protein in the genome, affected defecation behavior and daumone response. CFL-1 is highly homologous to the FBXL20 in mammals, which regulates synaptic vesicle release by targeting its substrate Rim1 for ubiquitin-mediated degradation. The worm homolog of Rim1 is UNC-10, a presynaptic membrane protein that triggers synaptic vesicle fusion through interaction with RAB-3 GTPase.

Gene Silencing and Haploinsufficiency of Csk Increase Blood Pressure.

Objective: Recent genome-wide association studies have identified 33 human genetic loci that influence blood pressure. The 15q24 locus is one such locus that has been confirmed in Asians and Europeans. There are 21 genes in the locus within a 1-Mb boundary, but a functional link of these genes to blood pressure has not been reported.

The xanthine oxidase-NFAT5 pathway regulates macrophage activation and TLR-induced inflammatory arthritis.

NFAT5 (nuclear factor of activated T cells), a well-known osmoprotective factor, can be activated by isotonic stimuli such as Toll-like receptor (TLR) triggering. However, it is unclear how NFAT5 discriminates between isotonic and hypertonic stimuli to produce different functional and molecular outcomes. Here, we identified a novel XO-ROS-p38 MAPK-NFAT5 pathway (XO is xanthine oxidase, ROS is reactive oxygen species) that is activated in RAW 264.

Microarray-based analysis of the differential expression of melanin synthesis genes in dark and light-muzzle Korean cattle.

The coat color of mammals is determined by the melanogenesis pathway, which is responsible for maintaining the balance between black-brown eumelanin and yellow-reddish pheomelanin. It is also believed that the color of the bovine muzzle is regulated in a similar manner; however, the molecular mechanism underlying pigment deposition in the dark-muzzle has yet to be elucidated. The aim of the present study was to identify melanogenesis-associated genes that are differentially expressed in the dark vs.

Effects of hormones on the expression of matrix metalloproteinases and their inhibitors in bovine spermatozoa.

Proteases and protease inhibitors play key roles in most physiological processes, including cell migration, cell signaling, and cell surface and tissue remodeling. Among these, the matrix metalloproteinase (MMPs) pathway is one of the most efficient biosynthetic pathways for controlling the activation of enzymes responsible for protein degradation. This also indicates the association of MMPs with the maturation of spermatozoa.

p53 controls autoimmune arthritis via STAT-mediated regulation of the Th17 cell/Treg cell balance in mice.

Objective: To investigate the connection between p53 and interleukin-17-producing Th17 cell/Treg cell balance in rheumatoid arthritis (RA).

Methods: Th17 cell and Treg cell frequencies were analyzed by flow cytometry, and cytokine levels in the supernatant were determined using enzyme-linked immunosorbent assays. The expression of transcription factors was analyzed by immunostaining and Western blotting, and the interactions between p53 and STAT-3 or STAT-5 were determined by immunoprecipitation-Western blot analysis.

Interleukin-2/anti-interleukin-2 monoclonal antibody immune complex suppresses collagen-induced arthritis in mice by fortifying interleukin-2/STAT5 signalling pathways.

In this study, we investigated the effects of administration of interleukin-2 (IL-2)/JES6-1 (anti-IL-2 monoclonal antibody) immune complexes on the expansion and activation of regulatory T (Treg) cells, the down-regulation of T helper type 17 (Th17) cells, and the control of the severity of collagen-induced arthritis (CIA). Wild-type and CIA-induced wild-type mice were injected intraperitoneally (i.p.

A distinct tolerogenic subset of splenic IDO(+)CD11b(+) dendritic cells from orally tolerized mice is responsible for induction of systemic immune tolerance and suppression of collagen-induced arthritis.

In oral tolerance, locally instigated tolerance in the gut propagate to systemic tolerance. In order to investigate the mechanism, we analyzed indoleamine 2,3-dioxygenase (IDO) expression in splenic dendritic cell (DC) subsets and tested whether DCs suppress collagen-induced arthritis (CIA) by inducing regulatory T cells (Tregs). The proportion of IDO-expressing cells was higher in the CD11b(+) subset of splenic DCs from orally tolerized CIA mice.

Aberrant phenotypes of transgenic mice expressing dimeric human erythropoietin.

Background: Dimeric human erythropoietin (dHuEPO) peptides are reported to exhibit significantly higher biological activity than the monomeric form of recombinant EPO. The objective of this study was to produce transgenic (tg) mice expressing dHuEPO and to investigate the characteristics of these mice.

Methods: A dHuEPO-expressing vector under the control of the goat beta-casein promoter, which produced a dimer of human EPO molecules linked by a 2-amino acid peptide linker (Asp-Ile), was constructed and injected into 1-cell fertilized embryos by microinjection.

Expression of aldo-keto reductase family 1 member C1 (AKR1C1) gene in porcine ovary and uterine endometrium during the estrous cycle and pregnancy.

Background: The aldo-keto reductase family 1 member C1 (AKR1C1) belongs to a superfamily of NADPH-dependent reductases that convert a wide range of substrates, including carbohydrates, steroid hormones, and endogenous prostaglandins. The 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD) is a member of AKR family. The aims of this study were to determine its expression in the ovary and uterus endometrium during the estrous cycle and pregnancy.

Molecular characterization of bovine placental and ovarian 20α-hydroxysteroid dehydrogenase.

The enzyme 20α-hydroxysteroid dehydrogenase (20α-HSD) catalyzes the conversion of progesterone to its inactive form, 20α-hydroxyprogesterone. This enzyme plays a critical role in the regulation of luteal function in female mammals. In this study, we conducted the characterization and functional analyses of bovine 20α-HSD from placental and ovarian tissues.

Control of asymmetric cell division in early C. elegans embryogenesis: teaming-up translational repression and protein degradation.

Asymmetric cell division is a fundamental mechanism for the generation of body axes and cell diversity during early embryogenesis in many organisms. During intrinsically asymmetric divisions, an axis of polarity is established within the cell and the division plane is oriented to ensure the differential segregation of developmental determinants to the daughter cells. Studies in the nematode Caenorhabditis elegans have contributed greatly to our understanding of the regulatory mechanisms underlying cell polarity and asymmetric division.

Genetic variations in the sodium balance-regulating genes ENaC, NEDD4L, NDFIP2 and USP2 influence blood pressure and hypertension.

Background/aims: In humans, the kidneys regulate blood pressure by balancing sodium concentrations. Fine-tuning of renal sodium reabsorption and excretion depends on the epithelial sodium channel protein (ENaC: protein complex of SCNN1A, SCNN1B, and SCNN1G). The surface expression of ENaC components is directed by the ubiquitination of ENaC by NEDD4L, an ENaC-specific E3 ubiquitin ligase, and is regulated by the deubiquitination of ENaC by USP2.

Characterization of a cryptic plasmid from an alpha-proteobacterial endosymbiont of Amoeba proteus.

A new cryptic plasmid pAP3.9 was discovered in symbiotic alpha-proteobacteria present in the cytoplasm of Amoeba proteus. The plasmid is 3869bp with a GC content of 34.

The dps gene of symbiotic "Candidatus Legionella jeonii" in Amoeba proteus responds to hydrogen peroxide and phagocytosis.

To survive in host cells, intracellular pathogens or symbiotic bacteria require protective mechanisms to overcome the oxidative stress generated by phagocytic activities of the host. By genomic library tagging, we cloned a dps (stands for DNA-binding protein from starved cells) gene of the symbiotic "Candidatus Legionella jeonii" organism (called the X bacterium) (dps(X)) that grows in Amoeba proteus. The gene encodes a 17-kDa protein (pI 5.

Antigen-induced, tolerogenic CD11c+,CD11b+ dendritic cells are abundant in Peyer's patches during the induction of oral tolerance to type II collagen and suppress experimental collagen-induced arthritis.

Objective: Although oral tolerance is a well-known phenomenon, the role of dendritic cells (DCs) is not well characterized. This study was conducted to better understand the differential role played by each Peyer's patch DC subset in the induction of oral tolerance to type II collagen (CII) in murine collagen-induced arthritis (CIA).

Methods: CII was fed 6 times to DBA/1 mice beginning 2 weeks before immunization, and the effect on arthritis was assessed.

Sensitization of vanilloid receptor involves an increase in the phosphorylated form of the channel.

A vanilloid receptor (VR1, now known as TRPV1) is an ion channel activated by vanilloids, including capsaicin (CAP) and resiniferatoxin (RTX), which are pungent ingredients of plants. Putative endogenous activators (anandamide and metabolites of arachidonic acid) are weak activators of VR1 compared to capsaicin and RTX, and the concentrations of the physiological condition of those activators are not sufficient to induce significant activation of VR1. One way to overcome the weak activation of endogenous activators would be the sensitization of VR1, with the phosphorylation of the channel being one possibility.

In vitro differentiation of mouse embryonic stem cells: enrichment of endodermal cells in the embryoid body.

Embryonic stem (ES) cells have the potential to differentiate into all three germ layers, providing new perspectives not only for embryonic development but also for the application in cell replacement therapies. Even though the formation of an embryoid body (EB) in a suspension culture has been the most popular method to differentiate ES cells into a wide range of cells, not much is known about the characteristics of EB cells. To this end, we investigated the process of EB formation in the suspension culture of ES cells at weekly intervals for up to 6 weeks.

Expression of IL-17 homologs and their receptors in the synovial cells of rheumatoid arthritis patients.

IL-17 is a major proinflammatory cytokine secreted by activated T-lymphocytes that accumulates in the inflamed joints of rheumatoid arthritis (RA) patients. Additional IL-17-related molecules and their receptors have been discovered and may also contribute to RA pathogenesis. We examined the expression of the prototypic IL-17 (IL-17A) and its homologs, IL-17B-F, by RT-PCR analyses of synovial fluid mononuclear cells (SFMCs) and peripheral blood mononuclear cells (PBMCs) from RA patients.

Induction of IL-10-producing CD4+CD25+ T cells in animal model of collagen-induced arthritis by oral administration of type II collagen.

Induction of oral tolerance has long been considered a promising approach to the treatment of chronic autoimmune diseases, including rheumatoid arthritis (RA). Oral administration of type II collagen (CII) has been proven to improve signs and symptoms in RA patients without troublesome toxicity. To investigate the mechanism of immune suppression mediated by orally administered antigen, we examined changes in serum IgG subtypes and T-cell proliferative responses to CII, and generation of IL-10-producing CD4+CD25+ T-cell subsets in an animal model of collagen-induced arthritis (CIA).

Increase of cyclooxygenase-2 expression by interleukin 15 in rheumatoid synoviocytes.

Objective: To determine the effect of interleukin 15 (IL-15) on cyclooxygenase-2 (COX-2) expression in rheumatoid synoviocytes.

Methods: Fibroblast-like synoviocytes (FLS) were prepared from the synovial tissues of patients with rheumatoid arthritis (RA) and cultured in the presence of IL-15. Levels of COX-2 mRNA and protein expression were determined by reverse transcription-polymerase chain reaction and Western blot, respectively.

The MCP-1 promoter -2518 polymorphism in Behcet's disease: correlation between allele types, MCP-1 production and clinical symptoms among Korean patients.

Objective: To compare the G vs. A variation at the MCP-1 promoter -2518 position among normal Koreans and Behcet patients, and to investigate possible association of this polymorphism with disease pathogenesis.

Methods: The allele type of -2518 polymorphism was determined by restriction fragment length polymorphism of Pvu II.

IL-17 induces production of IL-6 and IL-8 in rheumatoid arthritis synovial fibroblasts via NF-kappaB- and PI3-kinase/Akt-dependent pathways.

Recent studies of the pathogenesis of rheumatoid arthritis (RA) have revealed that both synovial fibroblasts and T cells participate in the perpetuation of joint inflammation as dynamic partners in a mutual activation feedback, via secretion of cytokines and chemokines that stimulate each other. In this study, we investigated the role of IL-17, a major Th1 cytokine produced by activated T cells, in the activation of RA synovial fibroblasts. Transcripts of IL-17R (IL-17 receptor) and IL-17RB (IL-17 receptor B) were present in fibroblast-like synoviocytes (FLS) of RA patients.