The differentiation and polarization of macrophages

have

The differentiation and polarization of macrophages

have been extensively studied, particularly with regard to transcriptional regulation. For instance, the PU.1 and C/EBP transcription factors are critical for the development of macrophages. M1 macrophage polarization by TLR ligands involves the activation of a set of transcription factors, such as NF-κB, AP-1, C/EBPβ, PU.1 and IFN-regulatory factors (IRFs) 6, 19. On the other hand, transcription factors such as STAT6 and peroxisome proliferator-activated receptor (PPAR)-γ are involved in the polarization of M2 macrophages 14, 20. However, recent studies have revealed that epigenetic regulation is also important for macrophage development and polarization. Epigenetic changes regulate diverse cellular functions including cellular differentiation, cell activation and transformation. Dynamic changes in DNA methylation and histone modifications Selleck BGJ398 are associated with altered gene expression 21. Although the epigenetic control

of macrophage function is not fully understood, GSK1120212 mw we here discuss several mechanisms that have become clearer recently. Methylation of the cytosine in the CpG dinucleotide is mediated by a number of DNA methyltransferases, and is generally associated with gene silencing by affecting the recruitment of transcription factors, which results in cellular differentiation 22. Global changes in DNA methylation in hematopoietic cell differentiation have been studied in the mouse BM 23, revealing that myeloid commitment from hematopoietic stem cells is associated with reduced global DNA methylation as compared with that during lymphoid commitment. After treatment with a DNA methyltransferase inhibitor, progenitors are skewed toward myeloid rather than lymphoid cells, suggesting that control of DNA methylation is important for myeloid cell differentiation. Although DNA methylation analysis in mature macrophages has not been reported, it was shown that the methylated

CpGs on the CD209 promoter were drastically demethylated following differentiation from monocytes to dendritic cells 24. Consistently, the expression of CD209, which encodes Wilson disease protein DC-SIGN, increased upon differentiation in human cells, suggesting that loss of the inhibitory epigenetic mark contributes to the differentiation of monocytes. Further studies in macrophages will be necessary for uncovering the role of DNA methylation regulation in macrophage polarization. It is widely accepted that histone modifications such as methylation, acetylation and phosphorylation are important for controlling gene expression, and specific combinations of modifications are considered to constitute a “histone code”. Histone acetylation marks are enriched in activated chromatin regions 25.

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trachomatis released from NK cell-exposed infected cells, pooled

trachomatis released from NK cell-exposed infected cells, pooled A2EN cell lysates and culture supernatants from C. trachomatis-infected cells cocultured with NK cells were compared with those cultured for the same period of time postinfection but in the absence of NK cells. The marked decrease in recoverable IFU from cells cocultured with NK92MI cells (Fig. 5; Fig. S1) suggests that these effector cells exert some degree of sterilizing effect on C. trachomatis-infected endocervical cells and that host NK cells could decrease the infectious burden during C. trachomatis infection. Surprisingly, however, we note that although efficient lysis of C. trachomatis-infected cells was observed

at 34 hpi, the observed decrease in IFU recovered was only twofold. These data suggest that C. trachomatis may be equipped with some form of escape mechanisms despite NK cell-mediated LDK378 datasheet lysis of its host cells. Infectious pathogens evade innate and adaptive host immune detection through modulation of host responses. Successful pathogens, including C. trachomatis, exert overlapping and redundant mechanisms that often include alterations in those host ligands that mediate interactions with innate and adaptive immune cells (Tortorella et al., 2000). While GW-572016 ic50 well-orchestrated, pathogen protective strategies would promote evasion of antigen nonspecific innate immunity and antigen-specific adaptive

responses, co-evolution of pathogen and host enable a balance between Alanine-glyoxylate transaminase pathogen evasion

and host protection. For C. trachomatis, we and others have shown that host cell MHC class I, Class II, and CD1d are degraded in infected cells relatively late in the pathogen’s developmental cycle (Zhong et al., 1999; : Zhong et al., 2000; : Zhong et al., 2001; Kawana et al., 2007, 2008). This occurs well after the initiation of chemokine/cytokine secretion by C. trachomatis-infected epithelial cells, which usually does not begin until 20–24 h after infection (Rasmussen et al., 1997). The latter delay may allow a window for unfettered pathogen growth and development. We have recently demonstrated that downregulation of cell surface expression of MHC class I in C. trachomatis-infected A2EN cells can be seen on infected cells and on bystander, noninfected cells in culture (Ibana et al., 2011a), which may further protect C. trachomatis pathogens from antigen-specific clearance. By harnessing our capability to assess the host epithelial cell response to C. trachomatis in both bystander-noninfected cells and C. trachomatis-infected cells, we now show that the effects on MHC class I and on MICA kinetically occur in tandem, beginning prior to 24 hpi and lasting until late in the developmental cycle. Unlike its effects on MHC class I, the effects of C. trachomatis on MICA expression include an upregulation of expression, effects that are significantly more prolonged (still rising at 42 hpi) and effects that are limited to infected cells.

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, 2006; Lifshitz et al , 2009) The tissue-protective and immunom

, 2006; Lifshitz et al., 2009). The tissue-protective and immunomodulatory functions of Epo on the one hand and erythropoiesis on the other are mediated by different EpoR (Brines et al., 2004; Brines & Cerami, 2008). The hematopoietic receptor is a homodimer of EpoR subunits with a very high affinity to Epo, corresponding to picomolar concentrations Z-VAD-FMK ic50 of circulating Epo. The tissue-protective receptor, in contrast, is a heterodimer consisting of one EpoR subunit disulfide-linked to the β common receptor (CD131). Its affinity for Epo is lower and local concentrations of Epo therefore need to be higher. Efforts have been made to design Epo analogues with confined receptor specificity, allowing tissue-protective, but

not erythropoietic activity (Brines et al., 2008). The pyroglutamate helix B surface peptide (ARA290) is a short peptide of 11 amino acids, designed for specificity to the EpoR–CD131 heterocomplex and without erythropoietic

function (Brines et al., 2008). The tissue-protective and lack of erythropoitetic activity have been reported for ARA290 with in vitro and animal studies. Here, we sought to investigate the influence of ARA290 on two parameters crucial for UTI pathogenesis, early immune response and cellular infection by UPEC, using a cell culture model of E. coli UTI. All cell lines were obtained from the American Type Culture Collection (ATCC, Manassas, VA) GSK-3 inhibitor review and maintained in an appropriate medium (Gibco, Carlsbad, CA) at 37 °C in a 5% CO2 and humidified atmosphere. The human bladder cell lines T24 (HTB-4) and 5637 (HTB-9) were cultured in McCoy’s medium and RPMI-1640 medium containing l-glutamine, respectively, supplemented with 10% fetal bovine serum. Primary human bladder epithelium progenitor cells were purchased from CELLnTEC (Bern, Switzerland). Cells were maintained in CnT-58 medium supplemented with antibiotics to final GNAT2 concentrations of 100 U mL−1 penicillin, 100 μg mL−1 streptomycin and 250 ng mL−1

amphotericin B (CELLnTEC) in a 5% CO2 and humidified atmosphere at 35 °C following the instructions of the supplier. For all the experiments, cells reaching confluence were used. The monocytic cell line THP-1 (TIB-202) was maintained in RPMI-1640 medium containing l-glutamine and supplemented with 10% fetal bovine serum, 1 mM HEPES and 0.05 mM 2-mercaptoethanol. In all the experiments, 106 THP-1 cells mL−1 were used. The E. coli cystitis strain NU14 was used for cell stimulation. Bacteria were grown in a static Luria–Bertani broth to enhance the expression of type 1 fimbriae and collected by centrifugation at 3500 g for 10 min. Bacteria were inactivated by the addition of gentamicin to the cell culture medium (40 μg mL−1) to allow longer stimulation without perturbing the viability of epithelial cells. Alternatively, bacteria were heat-inactivated when cells were used for subsequent infection assays. For this purpose, E.

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To identify new potential growth factors, we compared the express

To identify new potential growth factors, we compared the expression profile of IL-1β-stimulated ECs over 4, 8 and 16 h with non-stimulated ECs using oligonucleotide microarrays covering more than 46 000 transcripts. Most significant changes were detected after 4 h. Utilization of Gene Ontology annotation for the stimulated EC transcriptome indicated

multiple upregulated genes encoding extracellular proteins with a cell–cell signaling CHIR-99021 function. Using flow cytometry, delta, colony and cobblestone assays, we assessed the proliferative capacities of 11 gene products, i.e. IL-8, IL-32, FGF-18, osteoprotegerin, Gro 1–3, ENA78, GCP-2, CCL2 and CCL20, which are not known to induce HPC expansion. Notably, IL-32 and to a lesser degree osteoprotegerin and Gro 3 significantly induced the proliferation of HPCs. Furthermore, IL-32 attenuated chemotherapy-related BM cytotoxicities by increasing the number of HPCs in mice. Our findings confirm that the combination of microarrays and gene annotation helps to identify new hematopoietic growth factors. Endothelial cells (ECs) have been shown to support the proliferation AZD8055 solubility dmso of hematopoietic CD34+ progenitor cells by the constitutive

production of cytokines 1, 2. In previous studies, we demonstrated that ECs stimulated by TNF-α induced the generation of dendritic cells from CD34+ cells for more than 6 wk 3. ILs, on the other hand, Cytidine deaminase can also induce the proliferation of hematopoietic and myeloid progenitors 4. So far, GM-CSF and G-CSF are known to be secreted by IL-stimulated ECs 5. Other endothelial factors propagating progenitor expansion include stem cell factor (SCF) 6, leukemia inhibitory factor (LIF) 7 and IL-6 8, 9. Beyond the known cytokine scenario, ECs synthesize multiple other proteins 10, i.e. chemokines

of the C-X-C, C-C and TNF receptor superfamily; however, whether these factors can also support hematopoietic progenitor cell (HPC) expansion remains unknown. Notably, microarray technologies monitoring expression changes for thousands of genes have been the basis for several systematic studies of immune and stem cells and their involvement in a variety of processes 11–15. For example, microarrays of ECs helped to reveal unknown signaling pathways in the endothelial immune cascades 16, specify the role of inflammatory stimuli in neutrophil transmigration 17 and identify the effects of biochemical forces 18. Microarrays of cultured HPCs also defined detrimental components of engineered extracellular matrices 19. To use microarrays of feeder cells for the identification of new hematopoietic growth factors is another aspect. Choong et al., for example, discovered proliferin-2 after microarray analyses of several supportive stroma cell lines 20. Chute et al. used a similar approach when they discovered the hematopoietic activity of adrenomedullin expressed by human brain ECs 21.

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One patient with adynamic bone disease subsequently developed bio

One patient with adynamic bone disease subsequently developed biochemical recurrence of hyperparathyroidism. Serial bone densitometry showed remarkable improvement. There was no fracture. Conclusion:  In the studied series of total parathyroidectomy

without autoimplant, adynamic A-769662 research buy bone disease occurred in three out of seven repeat bone biopsies while improvement occurred in the rest. Bone mineral density was much improved and there was no fracture. “
“Nephrogenesis is dependent on the input of several transcriptional regulatory networks. However, the details of how these networks operate and converge to facilitate nephron progenitor specific programmes are largely unknown. To this end, recent studies have focused on identifying the precise regulatory mechanisms that modulate progenitor maintenance and induction. Continued focus on this area of research will help identify Cell Cycle inhibitor nephrogenic programmes which could be manipulated for therapeutic intervention of kidney disease. The eloquent progression of nephrogenesis during embryonic kidney development requires a careful balance of nephron progenitor self-renewal and differentiation. This ensures a sufficient number of nephrons are formed to carry out their essential roles in waste filtration and body fluid homeostasis. In mammals this is a terminal process; no resident progenitors remain after fetal or early neonatal

stages. De novo nephron formation does not appear to be an option for the adult mammalian kidney, necessitating repair of existing nephrons following injury or disease. In this light, developing alternative, knowledge-based strategies to induce de novo nephrogenesis is an important therapeutic goal. As a first step, we need to develop a thorough understanding of the nephron progenitor population and the underlying regulatory

programmes governing its maintenance and nephron-specific capabilities. Leveraging this knowledge base will spur the development of new strategies to treat the damaged and diseased Orotidine 5′-phosphate decarboxylase kidney. The mammalian kidney develops through reciprocal interactions of the ureteric epithelium with adjacent mesenchymal nephron progenitors. Signals from nephron progenitors support ureteric epithelial branching and the arborization of the urine transporting collecting duct network derived from this epithelium. In turn, the transition of multi-potent nephron progenitors into epithelial renal vesicles, the nephron precursor, requires signals from the ureteric bud. Over the last few decades, research efforts have uncovered a number of factors with integral roles in kidney development. In particular, the transcriptional regulators and associated components including: Six1, Pax2, Hox11 paralogs, Osr1, Sall1, Six2, Eya1 and Wt1 are all expressed within the nephron progenitors, and the depletion of each from the murine kidney results in insufficient kidney development.

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Here we report a rare case of IgG4RD that developed during chroni

Here we report a rare case of IgG4RD that developed during chronic hemodialysis. Case Report: A 61-year-old male with polycystic kidney disease who had been on hemodialysis for seven years was referred

to our hospital because of nausea, cough and asthma that recently appeared during hemodialysis BTK assay session. The symptoms continued even after dialyzers were changed to other ones. He had been having submaxillary gland swelling for five years. The blood tests showed eosinophilia (8000/ml), hypergammaglobulinemia (serum IgG 5462 mg/dl) with a rise in IgG4 concentration (1540 mg/dl). The biopsy of the gland revealed an

infiltration of plasma cells more than 50% of which being IgG4 positive without evidence of tumor, thus he was diagnosed as IgG4RD. No involvement was found in other organs including pancreas. Oral prednisolone (30 mg/day) was begun and the symptoms during hemodialysis immediately disappeared together with gradual improvement of eosinophilia and submaxillary gland swelling. Disussion and Conclusion: We should consider the possibility of IgG4RD when we see such patients on chronic hemodialysis showing episodic asthma and eosinophilia. EDAMATSU TAKEO, FUJIEDA AYAKO, EZAWA ATSUKO, ITOH YOSHIHARU Pharmaceutical Division, Kureha Corporation Introduction: Protein-bound

Temsirolimus ic50 retention solutes, which are known to be accumulated in the body of chronic kidney disease patients, are considered to have deleterious selleck chemical effects on disease progression. In fact, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), two representative molecules of such solutes, have been extensively studied to have harmful impacts related to renal and vascular function. Although considerable amount has been detected in hemodialysis patients, little study on other molecules, such as phenylsulfate (PhS), indoleacetic acid (IAA) and hippuric acid (HA), has been performed to date. Here we conducted a comparative study for such molecules to see how similar or dissimilar these compounds are. Methods: We evaluated effects of these compounds in LLC-PK1, a porcine renal tubular cell line. Effect on viable cell number was determined using WST-8, a water-soluble version of MTT. Effect on cell cycle progression was determined using propidium iodide (PI), after appropriate synchronization. Apoptotic cells were detected with Annexin V-FITC and PI. Protein and gene expression were determined by western blotting and real-time PCR, respectively. Results: All these compounds reduced cell number after 2 day incubation.

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For flow cytometry, the specific event acquisition gates were est

For flow cytometry, the specific event acquisition gates were established using appropriate isotype antibody controls.

Freshly obtained PBMC (1 × 105–2 × 106) or enriched CD19+ cells from freshly obtained PBMC were stained with human-specific antibodies, purchased from BD Biosciences unless noted otherwise. Antibodies for B cells were CD27 (clone M-T271), CD38 (clone HIT2), CD19 (clone SJ25C1), CD24 (clone ML5), CD5 (clone UCHT2), B220 (clone RA3-6B2), CD1d (clone CD1d142) and IL-10 (internal; JES3-19F1). We used the LIVE/DEAD cell viability reagent (Invitrogen) in all flow cytometry IWR 1 and FACS sorting to ensure that only live cells would be considered in the purification and in the analyses. When FACS was used to enrich DC or when DC were characterized by flow cytometry, we used Fc-Block pretreatment (BD Biosciences) prior to antibody staining. We used clone B-ly6 (BD Biosciences) for

CD11c-specific FACS and flow cytometry. To detect and enrich retinoic acid (RA)-producing DC from the GM-CSF/IL-4 cultures (cDC or iDC), we used the Aldefluor reagent (Stem Cell Technologies), a substrate of aldehyde dehydrogenases (ALDH) which are the rate-limiting enzymes for RA biosynthesis [34, 35]. In the presence of bioactive enzyme, the substrate is converted into a fluorescent product and cells with such bioactivity are readily detectable to facilitate cell sorting or flow cytometry. Cells were stained with CD11c-specific Autophagy activator antibodies and then co-treated as directed by the manufacturer with Aldefluor. The CD11c+Aldefluor+ cells were sorted by FACS, or their frequency was measured by flow cytometry. Freshly isolated PBMC (1 × 105–2 × 105), enriched CD19+ cells or specific B cell populations purified from freshly collected PBMC by FACS were placed into culture with or without an equal number of cDC, iDC or vehicle

control in RPMI-1640 with 10% fetal bovine serum (FBS), supplemented Histamine H2 receptor with 2 mM L-glutamine, 1 mM sodium pyruvate, 1× MEM-NEAA, 55 mM 2-mercaptoethanol and 100 μg/ml gentamicin (all purchased from Gibco-Invitrogen, Carlsbad, CA, USA). Proliferation of B cell populations was measured by flow cytometry [36-38] using a commercial 5-bromo-2-deoxyuridine (BrdU)+-containing kit (BrdU Flow Kit; BD Biosciences) in combination with antibodies to characterize the proliferating cells (antibodies as listed earlier). BrdU was added to individual wells on the final day of culture to a final concentration of 1 mM. We used the LIVE/DEAD cell viability reagent (Invitrogen) in all flow cytometry and FACS-sorting to ensure that only live cells would be considered in the purification and in the analyses.

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Following the cell cultures, the supernatants were collected for

Following the cell cultures, the supernatants were collected for measurements of IL-10 and TGF-β1 by enzyme immunoassay (EIA). Three-colour LY2109761 mouse flow cytometric analyses were performed at the optimal concentrations recommended by the manufacturer. Cells were stained with the appropriate antibodies for 15 min and washed three times with cold PBS, then analysed using an EPICS XL (Beckman Coulter, Tokyo, Japan), with 5000 events counted for each condition, and analysed using expo32™ software (Beckman Coulter). Isotype controls were used for

all of the samples. For intracellular cytokine staining, brefeldin A (Sigma-Aldrich) was added to the medium during the last 4 hr of the culture period. The cells were first stained with appropriate fluorescence antibodies to detect cell surface FDA-approved Drug Library high throughput markers, then fixed and permeabilized with Intraprep (Beckman Coulter,

Fullerton, CA). Cells were stained intracellularly with PE-conjugated anti-IL-10 or -TGF-β1. After washing, the cells were immediately subjected to flow cytometric analysis. The contents of IL-10 and TGF-β1 in culture media were measured using EIA, according to the manufacturer’s instructions. Briefly, appropriate sample amounts were transferred by pipette into the wells of anti-mouse IL-10- or TGF-β1-coated microtitre strips. Secondary biotinylated monoclonal antibodies were then added to the wells and incubated at room temperature for 90 min. After removing the excess secondary antibodies by washing, the samples were incubated with streptavidin-peroxidase. A substrate solution was added to produce colour directly proportional to the concentration of mouse IL-10 or TGF-β1 present in the sample. Quantitative results were obtained from a standard curve produced from the experimental findings. Total RNA was extracted from each sample of purified B cells using Isogen (Nippon Gene, Tokyo, Japan), then equal amounts of RNA were reverse transcribed into complementary DNA (cDNA) using a QPCR cDNA kit (Stratagene, La Jolla, CA).

All primers used were flanked Gefitinib by intron–exon junctions using the NCBI blast tool and primer3 software (Howard Hughes Medical Institute, MD). Primer sequences used for reverse transcription–polymerase chain reaction (RT-PCR) were as follows: IL-10; 5′-CAGCCGGGAAGACAATAACT-3′ and 5′-TCATTTCCGATAAGGCTTGG-3′, TGF-β1; 5′-TGCTTCAGCTCCACAGAGAA-3′ and 5′-TACTGTGTGTCCAGGCTCCA-3′, and glyceraldehyde 3-phosphate dehydrogenase (GAPDH); 5′-ACCCAGAAGACTCTGGATGG-3′ and 5′-GGTCCTCAGTGTAGCCCAAG -3′. Quantitative real-time PCR was performed using an ABI PRISM 7700 sequence detection system with SYBR Green PCR master mix (Applied Biosystems, Foster City, CA), according to the manufacturer’s instructions. The levels of IL-10 and TGF-β1 were normalized to that of GAPDH using sequence detector software (Applied Biosystems).

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Although level of pVL is closely associated with the rate of HIV

Although level of pVL is closely associated with the rate of HIV disease progression, it does not measure disease progression directly. We therefore calculated the rate

of decline in CD4+ T cell counts (see the Materials and Methods), and investigated their association with HLA allele expression as well, but failed to detect any alterations in the rate of decline as the HIV epidemic matured (data not shown). This may be due to the low statistical power of the present study, therefore larger scale studies are warranted in order to determine to what extent, and for which HLA alleles, such accumulations of CTL escape have been occurring, and how they have been affecting disease MG-132 manufacturer progression. In the present study, we have MAPK inhibitor demonstrated that: (1) there are no individual HLA class I alleles which are strongly associated with the level of pVL in the Japanese population at the current time; (2) the Japanese population has a narrow HLA distribution and lacks in the most protective HLA-B27/B57; (3) the proposed advantage of rare class I supertypes and the disadvantage of homozygotes

for Bw6 motif cannot be applied to all ethnic groups across the globe; and (4) HLA-B51 has been losing its dominant effects at the population level over time, whereas this is not the case for the other alleles. Despite substantial numbers of HIV-1 viremia controllers having been recognized in Japan, this population lacks the well-known protective alleles HLA-B27/B57. We therefore expected to discover novel associations between HIV disease progression and HLA class I alleles which are unique to Asian populations. However, in the cross-sectional analysis, we did not identify any significant associations between the level of pVL and expression of individual class I alleles, indicating

that, regardless of the geographical part of the world, the protective effects of HLA alleles are greatly biased to a few of the prominent alleles like HLA-B27/B57. The discordant results for HLA supertypes and homozygosity of the Bw6 motif between Japan and the USA are likely Dichloromethane dehalogenase also attributable to the lack of HLA-B27/B57 in the Japanese population. These two exceptional alleles are known to have targeting epitopes within Gag protein (10, 30–35). Likewise it has been suggested that expression of HLA alleles other than B27/57, but having targeting epitopes within Gag protein, are associated with lower pVL (8, 36–40). Therefore it is warranted to confirm that Gag specific CTL responses are associated with lower pVL in Japanese people who lack HLA-B27/57. In the cross-sectional analysis, we did not identify significant associations between pVL and HLA-A11, 26, B51 or Cw14 expression, all of which have been shown to be protective in Caucasians (7), However, subsequent analysis revealed that HLA-B51, at least, was protective in the past, indicating that there has been loss of targeting epitopes in the viral strains circulating in this population.

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trachomatis-infected cells in vitro (Rasmussen et al , 1997) Sti

trachomatis-infected cells in vitro (Rasmussen et al., 1997). Still, the fact that increases in MICA are Adriamycin seen only on infected cells but not on uninfected bystanders in the same culture suggests that soluble mediators are not sufficient for these effects. Chlamydia trachomatis infection mediates MHC class I downregulation

through direct mechanisms involving the degradation of the transcription factor, RFX5, by chlamydia protease-like activity factor (Zhong et al., 2000). We have previously demonstrated that ‘soluble factors’ could also mediate the downregulation of MHC class I (Ibana et al., 2011a). The downregulation of MHC class I by cytokines, including IL-10 (Caspar-Bauguil et al., 2000) and CXCL12 (Wang et al., 2008) has been demonstrated in other check details culture models, supporting our previous observation that MHC class I downregulation occurs indirectly in the bystander-noninfected cells present in C. trachomatis-infected A2EN cells (Ibana et al., 2011a). Cytokine-mediated induction of dendritic cell MICA transcription by IFNα has been reported (Jinushi et al., 2003), but the overall effects of cytokines on MICA expression appear to be quite pleiotropic with varying effects depending on cell

type and environment (reviewed in Champsaur & Lanier, 2010). In the present study, we observed that MICA is upregulated only in infected cells, demonstrating that the mechanisms underlying C. trachomatis-associated changes in MICA differ from those Selleck Rucaparib altering expression of MHC class I and suggesting C. trachomatis infection does not promote the production of soluble MICA-inducing mediators in our culture system. MICA was first described as cell stress-induced protein in the gastrointestinal epithelium (Groh et al., 1996). Increased MICA expression has been observed during both viral (cytomegalovirus) and

bacterial (M. tuberculosis) infections (Groh et al., 2001; Das et al., 2001). Our observation that upregulation of MICA was limited to C. trachomatis-infected cells may indicate that this induction is via infection-derived stress or danger signals that are absent in noninfected bystander cells. Currently, the exact mechanism underlying the induction of MICA expression during viral and bacterial infection is not completely understood. Interestingly, a recent study suggested that human microRNAs can regulate MICA expression, allowing the maintenance of MICA protein expression at a particular threshold while facilitating acute upregulation of MICA during cellular stress (Stern-Ginossar et al., 2008). If C. trachomatis infection induces MICA expression by interfering with the host microRNA-mediated control pathways, this may explain why MICA induction does not occur on uninfected bystander cells. The latter effect would protect the host from unwarranted NK cell activation.

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