Given that the Tsu is MHC-restricted and specific to NS-peptides, its normal role cannot be to regulate the S-NS discrimination [43, 44, 48]. However, it can be envisaged as a clinical tool to treat an autoimmune response by reducing its magnitude to below a pathological level. To understand how to use this tool, we must understand how tolerance is broken at the level of the Tsu (Treg) and how specificity for the

self-target is maintained. The general description filling the literature of a Treg population with an unsorted repertoire that nonspecifically shuts off responsiveness by secreting interleukins would be unable to regulate the magnitude of the effector response in an Eliminon-specific manner and, in no way, could be viewed as the tolerigenic mechanism used to make a S-NS discrimination (Module 2). In fact one might profitably ask, How is the S-NS discrimination Obeticholic Acid price accomplished for the Tsu (Treg) itself? These two experiments have been briefly

considered elsewhere [46], so that here a more detailed discussion of the consequences of possible outcomes will be considered. The question here is whether the switch from IgM to Ig-other is determined by a specific external signal BGB324 cost or is the switch random and the switched cells selected based on the functions of their expressed isotypes. Thus far, we have assumed the former. The vast majority of B cells are haplotype excluded at the H-chain locus by a rearrangement in-frame on one chromosome and out-of-frame on the other. This permits a probing experiment. Isolate by FACS or panning B cells expressing each of the Ig-isotypes from immune system experienced animals and determine to which C-gene segment (isotype) the unexpressed chromosome has rearranged. Consider an animal with seven isotypes: IgM, IgG1, IgG2, IgG3, IgG4, IgA and IgE. If the expressed and unexpressed (out-of-frame) chromosomes switch uniquely to the same isotype in every cell, then there would be one external signal per isotype, Acyl CoA dehydrogenase a total of seven in this illustration. This seems unlikely so one can expect some grouping of compatible isotypes into

ecosystems. Under one construct of the Trauma signalling Model, IgM cells would be expected to have their unexpressed loci rearranged to Cμ. If the IgG1-3 isotypes are grouped in the G-ecosystem, then the B cells expressing either IgG1 or IgG2 or IgG3 will each have their unexpressed haplotypes switched to a grouping of the same three isotypes. IgG4 might be in the A-ecosystem, in which case, IgA- or IgG4-expressing cells would have their unexpressed chromosomes switched to Cα or Cγ4. There exists the problem of possible secondary rearrangements, which would be unidirectional as switching deletes the C-exons in between. Switching from Cμ to Cε deletes Cμ and Cγ and switching to the distal Cα will delete all C-exons. As double switching is probably rare and there is an order, it should not confuse the analysis.

Cells were then plated in a 96-well plate with 2 × 105 cells per well (106 cells/ml), allowed to incubate for 60–90 min at 37° (+5% CO2), and re-stimulated with soluble anti-CD3ε (2·5 μg/ml) antibody. Following the indicated stimulation time, culture medium was collected and spun down to remove any residual cells. The concentration of IL-4, IL-6, IL-10, IL-17A, IFN-γ and tumour necrosis factor-α (TNF-α) in the cell-free culture medium was analysed using

custom bead arrays from Millipore, and quantified on a Luminex 100 system (Austin, TX) with the Luminex XY plate handling platform. Assays were performed according to the manufacturer’s protocols. Duplicate wells were assayed for each sample, and data are representative of the average median

value for each sample. Analysis was performed Trichostatin A chemical structure using is 2.3 software (Luminex). A vehicle consisting of 90% emulsion solution (PBS + 0·9% Tween-20 + 0·9% BSA) and 10% ethanol was used. For delivery of compounds, E2 or G-1 was dissolved in ethanol www.selleckchem.com/products/VX-809.html and added at appropriate concentrations such that 100 μl per animal per injection was used. The compound was added to each injection as part of the 10% ethanol found in the vehicle, so it was diluted such that < 10 μl per animal per injection was required. Injections were administered in the afternoon, and to limit stress from the long series of injections inherent in this study, animals were sedated using isofluorane before injection. Compound was delivered this website subcutaneously on the dorsum adjacent to the hind limb, and the side of the injection was alternated every 2 days. To investigate the direct effects of G-1 on CD4+ T cells, we chose to use purified cultures of naive T cells activated by polyclonal stimulation with anti-CD3ε and anti-CD28 antibody. This eliminated secondary effects caused by the activity of G-1 on APCs within the culture. Furthermore, primary cells from male mice were used

throughout the study to avoid potential confounding effects of either; (i) varying estrogen levels in female mice, or (ii) the inflammatory effects of ovariectomy. We have also determined that CD4+ CD44loCD62Lhi naive T-cell and CD4+ Foxp3+ T-reg cell populations express the G-1 target GPER (R. L. Brunsing and E. R. Prossnitz, manuscript in preparation). Given that G-1 can protect mice from EAE38,39 and the importance of the the Th17 lineage to this model,3 we began by determining the effects of G-1 on naive T-cell differentiation under Th17-polarizing conditions (TGF-β/IL-6 ± IL-23). Hence, naive T cells from 7- to 11-week-old male C57BL/6 mice were collected by FACS and stimulated for 4 days ex vivo, supplemented with combinations of TGF-β, IL-6 and IL-23. Following 4 days of stimulation, cells were analysed for expression of IFN-γ, IL-17A and IL-10 by intracellular cytokine staining. Expression of IL-10 was present exclusively in cultures treated with IL-6 (Fig.

There were Selleckchem Tyrosine Kinase Inhibitor Library no significant alterations in the percentage of pre-pro, pro-, pre-, immature and mature B-cell populations (Fig. 5c) based upon published cell surface markers.[24, 25] Furthermore, while B-cell development is also dependent upon IL-7 in the mouse,[30] there were no differences in IL-7Rα expression in the bone marrow B-cell subsets (Fig. 5d). Down-regulation of IL-7Rα protein expression

in the thymus was, at least in part, transcriptional because quantitative PCR analysis of total thymocytes indicated a nearly twofold decrease in IL-7Rα mRNA levels (Fig. 6a). Another potential mechanism for decreased IL-7Rα expression could be a result of the ‘altruistic’ down-regulation of the receptor by increased concentrations of the ligand IL-7 produced by thymic stromal cells.[31] However, there was no increase in IL-7 mRNA expression in total thymus from Ts65Dn mice compared with euploid controls (Fig. 6b). Previous data have suggested that

increased oxidative stress, potentially linked to decreased reduced glutathione levels, induced a loss of IL-7Rα expression in bone marrow haematopoietic progenitors.[6] Consistent with this observation, reduced glutathione, measured with MCB, was significantly decreased in immature, DN Ts65Dn thymocytes, but not in the total thymocytes, in comparison to euploid controls Selleck Smoothened Agonist (Fig. 7a). In addition, consistent with previous observations in haematopoietic stem cells and bone marrow lymphoid progenitors,[6] DN thymocytes exhibited enhanced oxidation of the redox-sensitive dye DCFDA (Fig. 7b), whereas there was little increase in DP thymocytes and no significant increase in DCFDA oxidation in splenic T cells (not shown). Hence, increases in oxidative stress may be linked to decreased IL-7Rα expression and function in the thymus as well. One triplicated gene in DS potentially linked to

oxidative stress is BACH1, and increased levels of BACH1 have been described in tissues from individuals Methane monooxygenase with DS.[32] BACH1, reported to be well expressed in thymus,[33] inhibits Nrf2-mediated induction of antioxidant gene expression through antioxidant response elements (ARE). NAD(P)H:quinone oxidoreductase1 (NQO1) is an antioxidant flavoprotein that is a known target and established marker of Nrf-2 activation.[34] NQO1 expression was decreased twofold in Ts65Dn thymuses (Fig. 7c) and Lin− bone marrow (Fig. 7d) in comparison with euploid controls. Deficient NQO1 induction is consistent with decreased Nrf2-mediated antioxidant response induction in Ts65Dn thymocytes and haematopoietic progenitors, which may cause increased oxidative stress and contribute to haematopoietic progenitor and thymic dysfunction. It is unclear whether oxidative stress affects IL-7Rα transcription, but inhibition of the Notch signalling pathway was shown to down-regulate IL-7Rα expression in T-cell lineage, but not B-cell progenitors.

4, Supplementary Fig. S2). TF release by cells stimulated with IgG fractions from SN-APS, LPS or IgG fractions from APS was increased significantly compared to untreated endothelial cells, as well as cells stimulated with human control IgG. TF release was Liproxstatin-1 clinical trial inhibited significantly by preadsorption of SN-APS IgG with CL or LBPA (Fig. 4). To our knowledge, this is the first study showing aPL detected by TLC immunostaining associated with clinical features of APS in patients repeatedly negative for the laboratory criteria of APS, i.e. aCL, aβ2-GPI and LA. Moreover, the results suggest that the biological activity of these antibodies is able to trigger a signal transduction pathway(s) in endothelial cells with consequent proinflammatory

and procoagulant effects. Current laboratory criteria for the classification PLX-4720 molecular weight of APS include aCL and aβ2-GPI measured by standardized ELISA and LA, detected by clotting assays [1,21]. However, the term SN-APS has been suggested recently for patients with a clinical profile suggestive of APS who are persistently negative for the routinely used assays [2,22,23]. We studied here a cohort of patients affected mainly by autoimmune systemic diseases presenting a clinical picture suggestive of APS, i.e. vascular thrombosis and/or pregnancy morbidity associated with several non-criteria APS features, persistently negative for the routinely used aPL. Interestingly, a statistically significant

correlation was observed between thrombosis and pregnancy morbidity in these patients. In the absence of positive blood tests, more clinical features would make a diagnosis of SN-APS more convincing. We identified the presence of aPL in about 60% of such patients using a method (TLC immunostaining) in which the antigen was run on aluminium-backed silica gel plates; in this way it may mimic phospholipid exposure after protein binding [8,12]. Interestingly, a strong correlation Oxaprozin was observed between these aPL specificities demonstrated by TLC immunostaining. The prevalence of aPL detected by TLC test in SLE patients without APS was similar to that showed by ELISA (61% and 78%, respectively). Although these aPL antibodies are probably

of low affinity and are not associated with any clinical manifestation, long-term prospective studies could clarify their clinical relevance. With regard to the so-called SN-APS patients, the discrepancies between ELISA and immunostaining on TLC plates in detecting antibodies against CL, LBPA and PE may be due to the different antigenic presentation of phospholipids on chromatograms compared to the surface of microtitre wells. In addition, six (16·7%) of the SN-APS patients showed serum IgG antibodies against annexin II detected by ELISA. Anti-annexin II have been associated recently with thrombosis in patients with APS, even though they can be detected in serum of patients with rheumatoid arthritis and other autoimmune systemic disorders [14,24].

In fact, plasmacytoid DCs have just been found to secrete substantial amounts of IL-4-producing Selleckchem VX-809 Th2 cells [27, 38]. Cytokine secretion was abrogated by the addition of MDR1 and MRP1 inhibitors. The inhibition of

DC maturation through ABC transporter blockers probably has a downstream impact on cytokine release. These findings allow us to suggest that the modulation of different DC phenotype profiles depends upon the initial stimulus and defines subsequent diverse cytokine activators, markers and functions. This is the first time that the role of ABC blockers as inhibitors of DCs maturation after hypoxia and LPS stimuli has been described. The impact of this immune activation, depending on DC maturation stimulus leading Belinostat clinical trial to different lymphocyte subtype proliferation, confirms the plasticity

of the immunological response in the face of pathological stimuli. In addition, both ABC transporter MDR1 and MRP1 blockers interfere in DC differentiation and maturation, modifying mature DC phenotype and lymphocyte activation. ABC transporters could be a potential target in DC-based immunosuppressive therapies designed to abrogate innate immune response when it is activated after ischaemia or endotoxin stimulus. The cellular and molecular mechanisms underlying the innate adaptive immune response to ischaemia–reperfusion are an active area of research with much more to tell us. These findings add more information about the specific functional role of ABC

transporters as a potential therapeutic target in alloimmunity modulation. We are especially grateful to the Servei Cientific-Tècnic team (Esther Castaño, Eva Julià and Benjamín Torrejón) and Nuria Bolaños and Cristian Varela for the technical support in immunological analyses. We thank Novartis in Basel for kindly providing PSC833. This study was supported by Astellas European Foundation Award (13th European Society of Transplantation), Instituto de Salud Carlos III (CP06/00067), Universitat de Barcelona and the Ministerio de Sanidad y Consumo (FIS PI07/0768 and PS09/00897). None. “
“Chronic helminth infections induce T-cell hyporesponsiveness, which may affect immune responses to other pathogens or to vaccines. This study Morin Hydrate investigates the influence of Treg activity on proliferation and cytokine responses to BCG and Plasmodium falciparum-parasitized RBC in Indonesian schoolchildren. Geohelminth-infected children’s in vitro T-cell proliferation to either BCG or pRBC was reduced compared to that of uninfected children. Although the frequency of CD4+CD25hiFOXP3+ T cells was similar regardless of infection status, the suppressive activity differed between geohelminth-infected and geohelminth-uninfected groups: Ag-specific proliferative responses increased upon CD4+CD25hi T-cell depletion in geohelminth-infected subjects only.

We thank Ministerio de Educación y Ciencia and FECYT (Spain) for a postdoctoral fellowship to O. Palomares. Conflict of interest: The authors declare no financial or commercial conflict of interest. “
“Citation Rosenberg VA, Buhimschi IA, Dulay AT, Abdel-Razeq SS, Oliver EA, Duzyj CM, Lipkind H, Pettker CM, Buhimschi CS. Modulation of amniotic fluid activin-A and inhibin-A in women with preterm premature rupture of the membranes and infection-induced preterm birth. Am J Reprod Immunol 2012; 67: 122–131 Problem  Activins and inhibins are important modulators of inflammatory processes. We explored activation of amniotic fluid (AF) activin-A and inhibin-A system in women with intra-amniotic

infection and preterm

premature rupture of the membranes (PPROM). Method of study  We analyzed 78 AF samples: ‘2nd trimester-control’ (n = 12), ‘3rd trimester-control’ see more (n = 14), preterm labor with intact membranes [positive-AF-cultures (n = 13), negative-AF-cultures (n = 13)], and PPROM [positive-AF-cultures (n = 13), negative-AF-cultures (n = 13)]. Activin-A levels were evaluated ex-vivo following incubation of amniochorion and placental villous explants with Gram-negative lipopolysaccharide (LPS) or Gram-positive (Pam3Cys) bacterial mimics. Ability of recombinant activin-A and inhibin-A to modulate inflammatory reactions in fetal membranes was explored through explants’ IL-8 release. Cyclopamine concentration Results  Activin-A and inhibin-A were present in human AF and were gestational age-regulated. Activin-A

was significantly upregulated by infection. Lower inhibin-A levels were seen in PPROM. LPS elicited release of activin-A from amniochorion, but not from villous explants. Recombinant activin-A stimulated IL-8 release from amniochorion, an effect that was not reversed by inhibin-A. Conclusion  Human AF activin-A and inhibin-A are involved in biological processes linked to intra-amniotic infection/inflammation-induced IMP dehydrogenase preterm birth. “
“National Institute for Medical Research, London, UK Cancer Research UK London Research Institute, London, UK The early growth response (Egr) transcription factor family regulates multiple steps during T-cell development. We examine here the role played by Egr2 in positive selection. In double-positive cells, Egr2 is upregulated immediately following TCR ligation, and its expression requires both the MAPK and calcineurin signaling pathways. Inducible transgenic and knockout mice were generated to cause gain- or loss-of-function of Egr2 in double-positive cells, and had reciprocal effects; more mature single-positive cells were made when Egr2 was overexpressed, and fewer when Egr2 was absent. These defects were associated with changes in the survival of positively selected cells rather than perturbation of positive selection or immediate post-selection signaling.

LAB have health-promoting effects, manifested through enhanced host immune responses due to increased production of NO and cytokines by macrophages (2). Thus, LAB are widely used as food supplements or therapeutic agents for several infectious diseases (3). Macrophages are phagocytes that reside within host tissues. These cells differentiate from monocytes and play an important role in host immune

responses (4). Various stimuli, including bacteria, LPS, lymphokines and interferons activate macrophages selleck chemical by (5). Activated macrophages regulate host immunity by secreting NO and inflammatory cytokines such as IL-1β and TNF-α (6, 7). NO, which is synthesized from L-arginine by the enzyme NO synthetases, is a short-lived mediator that either kills or inhibits the growth of bacteria and tumor cells (8, 9). IL-1β is a proinflammatory cytokine that induces a variety of cellular responses, including cell proliferation, differentiation, and apoptosis. It also triggers a cascade of immune responses by inducing expression/secretion CP-690550 cell line of other cytokines and chemokines (10, 11).

TNF-α has a broad spectrum of systemic and cellular activity and mediates resistance to infectious disease by suppressing intracellular pathogens and controlling inflammatory processes (12). Enterococcus faecium, Gram-positive cocci belonging to the genus Enterococcus, often occurs in pairs (diplococci) and are a commensal organism commonly found in the intestines. Enterococci are facultative anaerobic organisms, that is, they prefer to use oxygen but they can survive in the absence of oxygen when necessary (13). Administration of E. faecium enhances innate and acquired immune responses

in dogs and mice (14, 15). The immunomodulatory properties of LGG have been well-described. Early studies reported that LGG induces increased dendritic cell expression of IL-12, IL-17 and TNF-α (16) and that Methane monooxygenase peripheral blood mononuclear cells or macrophages co-cultured with Mycobacterium tuberculosis antigen release NO and IFN-γ (17). The objective of the present study was to investigate the immunomodulatory properties of E. faecium strain JWS 833, and its possible use as a feed-additive. JWS 833 was killed by heating and its immunomodulatory properties regarding NO and cytokines production by C57BL/6 peritoneal macrophages examined in vitro. Furthermore, the protective effects of JWS 833 were examined in vivo using a murine model of L. monocytogenes. The effects in in vitro and in vivo were compared with those mediated by LGG (ATCC 53103). JWS 833 and LGG were each grown in MRS broth (BD, Sparks, MD, USA) at 37°C for 24 hrs and viable cells (cfu/mL) on the MRS agar plates counted (BD). The bacterial cells were collected by centrifugation at 14,300 g for 10 mins at 4°C and the culture supernatant discarded.

In the present study, we demonstrated that infant mice were more susceptible to microbial sepsis. When infected with live bacteria or challenged with a clinically relevant, cecal slurry-induced polymicrobial sepsis, infant mice displayed a significantly higher mortality rate than adult mice. As one of the fundamental functions of the host innate immunity during microbial infection is to rapidly eradicate the invaded pathogens from the body [33], we further examined bacterial

clearance in infant mice after septic challenges. Consistent with an increased susceptibility to microbial sepsis, infant mice showed delayed https://www.selleckchem.com/products/GDC-0980-RG7422.html and reduced bacterial clearance from the circulation and visceral organs post septic challenges, with significantly higher bacterial counts in the blood, liver, spleen, and lungs compared with adult mice. This defect in bacterial clearance by infant mice is likely to have been underestimated when considering the total amount of bacteria or cecal contents injected between infant and adult mice. Infant mice in response to microbial infection; however, produced comparable proinflammatory cytokines to those of adult mice, which is somewhat discordant with studies in both murine and human neonates [26, 34-36] where significantly

reduced inflammatory cytokines were observed in neonates compared with adults. This discordance might be due to a more matured ability of immune cells to produce inflammatory cytokines in infants compared with neonates. Indeed, other studies have revealed that stimulus-induced production of several inflammatory Small molecule library cell assay cytokines by neonatal monocytes and APCs is equal to or even exceeds that of adults [37, 38].

These results indicate that, despite an appropriate proinflammatory cytokine production in response to microbial infection in infant mice, the antimicrobial response of their host innate immunity is defective and thus less efficient. Innate phagocytes including Arachidonate 15-lipoxygenase PMNs and macrophages form the first line in the host defense against microbial infection. However, in contrast to the well-described deficiencies in adaptive immunity, the innate immune response and in particular the innate phagocyte-associated antimicrobial function in neonates and infants during microbial sepsis remains poorly defined. PMN influx from the circulation into the infectious site plays a key role in eradicating the invaded microbial pathogens [27] and successful clearance of bacterial infection has been shown to rely on a rapid and efficient PMN migration into the infectious site such as peritoneal cavity in several experimentally established murine polymicrobial sepsis models [39-41]. Therefore, a defective and/or reduced recruitment of PMNs into the infectious site may account, at least in part, for the impaired bacterial clearance and increased susceptibility to microbial sepsis observed in infant mice.

6a, bottom panels). In some sections, single hepatocytes were found to be necrotic: a hallmark for ongoing liver injury. In contrast to the NRG mice, infiltrates were less pronounced in NRG Aβ–/–DQ8tg mice, also showing far fewer CD8+ T cells (Fig. 6a). Non-humanized mice (non-hu) showed no infiltrates (Fig. 6a, top panels). The skin is a further organ affected typically by GVHD. In both mouse strains we observed macroscopically alterations of skin texture such as hyperkeratosis, selleckchem scleroderma and desquamation, as

used for clinical score grading. As expected, histological examination confirmed these observations. The skin surface appeared undulated and signs of fibrosis, folliculitis and steatitis were evident within the hypodermis [see arrows in Fig. 6, haematoxylin

and eosin (H&E) staining]. Notably, these observations tended to be more severe in NRG control mice compared to NRG Aβ–/–DQ8tg mice. EPZ-6438 nmr As GVHD is a systemic disease, we consequently also detected huCD8 T cells in other organs, such as kidney and intestine. Again, infiltrates were less pronounced in NRG Aβ–/–DQ8tg mice compared to NRG mice (Fig. 6a). To quantify the huCD8+ cell infiltrates we used a published score [33]. Livers of NRG mice exhibited a significantly higher infiltration by human CD8+ T cells (mean score: Celecoxib 2·15) compared to those of NRG Aβ–/–DQ8tg mice (mean score: 1·36). In addition, kidneys and intestines of NRG mice were also infiltrated more severely by huCD8+ cells (mean score: 1·05 and 1·00, respectively) compared to NRG Aβ–/–DQ8tg mice (mean score: 0·58 and 0·42, respectively). This tendency of a more pronounced infiltration in NRG mice was also seen for the skin, although the difference was not statistically

significant (mean score: 1·45 versus 1·33 in NRG versus NRG Aβ–/–DQ8tg mice, respectively). Taken together, the delayed onset and mild progression of GVHD in NRG Aβ–/–DQ8tg mice could be due to a delay in the activation and expansion of xenoreactive CD8+ cells. In this study, we examined the effect of replacing murine MHC class II by HLA class II (DQ8) on the development of GVHD upon adoptive transfer of DQ8-positive human PBMCs into immunodeficient recipient mice (NRG Aβ–/–DQ8tg versus conventional NRG mice). The presence of HLA-DQ8 in NRG Aβ–/–DQ8tg recipient mice augmented significantly the overall repopulation rate by human PMBCs compared to conventional NRG mice. The cellular subset capable of engraftment was skewed exclusively towards CD3+ T cells in both mouse strains. Despite this, the striking difference between the two strains was the time-frame until GVHD became fatal.

Background: Increased urinary excretion of albumin is a marker of cardiovascular and renal disease. Albumin is highly

susceptible to modification via AGE, especially in the diabetic milieu Modification of albumin via AGE may alter the flux of albumin across the kidney and contribute to renal disease in diabetes. Methods: Trafficking of AGE-modified albumin (AGE-Alb) and unmodified Alb in RAGE (deficient; RAGE −/−) and AGE-R1 (overexpressing; AGE-R1 KI) was studied over time using Near Infrared IVIS/MRI imaging and confocal microscopy. Results: Wild type (WT) mice had the capacity to transport AGE-Albumin across the kidney which was greater than for unmodified albumin, with some urinary AGE-Alb detected >30kDa. By contrast RAGE−/− mice Torin 1 solubility dmso did not transport AGE-Alb into the kidney or across the renal filtration barrier but retained Alb transport. RAGE −/− mice had higher circulating AGE levels than WT but little trafficked AGE-Alb in the kidney. AGE-R1 KI

mice, trafficked more AGE-Alb and at an increased rate across the kidney when compared to WT mice or unmodified Alb. In contrast to WT, AGE-R1 KI mice also had very low circulating but higher urinary AGE concentrations and deposition of Near-IR AGE-Alb in the kidney. Renal function (determined by CrCl/UAER) was better in RAGE−/− but decreased GPCR Compound Library in AGE-R1 KI mice as compared with WT mice. Conclusion: Overall, this study suggests that increasing AGE-Alb flux into the urine decreases renal function. 170 FUNCTION OF RAGE AND MICRORNA IN MESANGIAL CELLS S HAGIWARA1, A MCCLELLAND1, E BRENNAN E1, JM FORBES2, ME COOPER1, P KANTHARIDIS1 Fossariinae 1JDRF Danielle Alberti Memorial Centre for Diabetic Complication, Diabetes Division, Baker IDI Heart and Diabetes

Institute, Melbourne, Victoria; 2Glycation & Diabetes, Mater Medical Research Institute, South Brisbane, Queensland, Australia Aim: We studied the role of RAGE in mouse mesangial cells (MMC) and the role of microRNAs in RAGE signaling. Background: MicroRNA (miRNAs) are a novel class of non-coding RNA that regulate gene expression post-transcriptionally by cleavage or translational repression of target mRNAs. It has been established that miRNAs play a role in the development and progression of diabetic nephropathy. Also, interaction of advanced glycation end products (AGEs) and their receptor (RAGE) activates multiple intracellular signaling pathways.