scholarly journals Glucocorticoids inhibit macrophage differentiation towards a pro-inflammatory phenotype upon wounding without affecting their migration

2018 ◽  
Author(s):  
Yufei Xie ◽  
Sofie Tolmeijer ◽  
Jelle Oskam ◽  
Tijs Tonkens ◽  
Annemarie H. Meijer ◽  
...  
Keyword(s):  
Small Subset ◽  
Transcriptional Responses ◽  
Zebrafish Model ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Inflammatory Phenotype ◽  
Transcriptional Changes ◽  
M1 Phenotype ◽  
A Site ◽  
Migration Of Macrophages

AbstractGlucocorticoid drugs are widely used to treat immune-related diseases, but their use is limited by side effects and by resistance, which especially occurs in macrophage-dominated diseases. In order to improve glucocorticoid therapies, more research is required into the mechanisms of glucocorticoid action. In the present study, we have used a zebrafish model for inflammation to study glucocorticoid effects on the innate immune response. In zebrafish larvae, the migration of neutrophils towards a site of injury is inhibited by the synthetic glucocorticoid beclomethasone, while migration of macrophages is glucocorticoid resistant. We show that wounding-induced increases in expression of genes encoding neutrophil-specific chemoattractants (Il8 and Cxcl18b) are attenuated by beclomethasone, but that beclomethasone does not attenuate the induction of the genes encoding Ccl2 and Cxcl11aa, which we show to be required for macrophage recruitment. RNA sequencing on Fluorescence-Activated Cell Sorting (FACS)-sorted macrophages showed that the vast majority of the wounding-induced transcriptional changes in these cells are inhibited by beclomethasone, whereas a small subset is glucocorticoid-insensitive. As a result, beclomethasone decreases the number of macrophages that differentiate towards a pro-inflammatory (M1) phenotype, which we demonstrated using atnfa:eGFP-Freporter line and analysis of macrophage morphology. We conclude that the glucocorticoid resistance of the wounding-induced macrophage migration is due to the insensitivity of the induction of macrophage-specific chemoattractants to glucocorticoid inhibition, which may explain the relative resistance of macrophage-dominated diseases to glucocorticoid therapy. However, the induction of pro-inflammatory genes in macrophages is strongly attenuated, which inhibits their differentiation to an M1 phenotype.Summary statementIn a zebrafish model for inflammation, glucocorticoids do not affect the migration of macrophages, but inhibit differentiation towards an M1 phenotype, by strongly attenuating transcriptional responses in these cells.

scholarly journals Role of the cytoskeleton in muscle transcriptional responses to altered use

2013 ◽  
Vol 45 (8) ◽  
pp. 321-331 ◽  
Author(s):  
Gretchen A. Meyer ◽  
Simon Schenk ◽  
Richard L. Lieber
Keyword(s):  
Mechanical Response ◽  
Fiber Type ◽  
Transcriptional Response ◽  
Primary Component ◽  
Transcriptional Responses ◽  
Expression Of Genes ◽  
Elevated Expression ◽  
Transcriptional Changes ◽  
Type Shift ◽  
Future Work

In this work, the interaction between the loss of a primary component of the skeletal muscle cytoskeleton, desmin, and two common physiological stressors, acute mechanical injury and aging, were investigated at the transcriptional, protein, and whole muscle levels. The transcriptional response of desmin knockout ( des −/−) plantarflexors to a bout of 50 eccentric contractions (ECCs) showed substantial overlap with the response in wild-type ( wt) muscle. However, changes in the expression of genes involved in muscle response to injury were blunted in adult des −/− muscle compared with wt (fold change with ECC in des −/− and wt, respectively: Mybph, 1.4 and 2.9; Xirp1, 2.2 and 5.7; Csrp3, 1.8 and 4.3), similar to the observed blunted mechanical response (torque drop: des −/− 30.3% and wt 55.5%). Interestingly, in the absence of stressors, des −/− muscle exhibited elevated expression of many these genes compared with wt. The largest transcriptional changes were observed in the interaction between aging and the absence of desmin, including many genes related to slow fiber pathway (Myh7, Myl3, Atp2a2, and Casq2) and insulin sensitivity (Tlr4, Trib3, Pdk3, and Pdk4). Consistent with these transcriptional changes, adult des −/− muscle exhibited a significant fiber type shift from fast to slow isoforms of myosin heavy chain ( wt, 5.3% IIa and 71.7% IIb; des −/−, 8.4% IIa and 61.4% IIb) and a decreased insulin-stimulated glucose uptake ( wt, 0.188 μmol/g muscle/20 min; des −/−, 0.085 μmol/g muscle/20 min). This work points to novel areas of influence of this cytoskeletal protein and directs future work to elucidate its function.

Regulation of cyanobacterial CO2-concentrating mechanisms through transcriptional induction of high-affinity Ci-transport systems

2005 ◽  
Vol 83 (7) ◽  
pp. 698-710 ◽  
Author(s):  
Fiona J Woodger ◽  
Murray R Badger ◽  
G Dean Price
Keyword(s):  
Carbon Fixation ◽  
Transport Systems ◽  
Transcriptional Level ◽  
Transcriptional Responses ◽  
High Affinity ◽  
Genetic Components ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Synechococcus Pcc7942 ◽  
Sense And Respond

Approximately 50% of global CO2-based productivity is now attributed to the activity of phytoplankton, including ocean-dwelling cyanobacteria. In response to inherent restrictions on the rate of CO2 supply in the aquatic environment, cyanobacteria have evolved a very efficient means of capturing inorganic carbon (Ci), as either CO2 or HCO3–. for photosynthetic carbon fixation. This capturing mechanism, known as a CO2-concentrating mechanism (CCM), involves the operation of active CO2 and HCO3– transporters and results in the concentration of CO2 around RuBisCO, in a unique microcompartment called the carboxysome. The CCM exhibits two basic physiological states: a constitutive, low-affinity state; and a high-affinity state, which is induced in response to Ci limitation. Many of the genetic components of the CCM, including genes encoding Ci transporters, have been identified. It is apparent that the expression of genes encoding the inducible, high-affinity Ci transporters is particularly sensitive to Ci availability, and we are now interested in defining how cyanobacterial cells sense and respond to Ci limitation at the transcriptional level. Current theories include direct sensing of external Ci; sensing of internal Ci-pool fluctuations; and detection of changes in photorespiratory intermediates, carbon metabolites, or redox potential. At present, there is no consensual view. We have investigated the physiological and transcriptional responses of CCM mutants and wildtype strains to pharmacological treatments and various light, O2, and Ci regimes. Our data suggest that perception of Ci limitation by a cyanobacterial cell is either directly or indirectly related to the size of the internal Ci pool within the cell, in an oxygen-dependent manner.Key words: CO2-concentrating mechanisms, CO2 sensing, Ci transporters, Synechococcus PCC7942.

scholarly journals NtbHLH1, a JAF13-like bHLH, interacts with NtMYB6 to enhance proanthocyanidin accumulation in Chinese Narcissus

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yuxin Fan ◽  
Jiayu Peng ◽  
Jiacheng Wu ◽  
Ping Zhou ◽  
Ruijie He ◽  
...  
Keyword(s):  
Flavonoid Biosynthesis ◽  
Transcriptional Level ◽  
Flavonoid Pathway ◽  
Regulation Of Expression ◽  
Over Expression ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Regulatory Complex ◽  
Positive Regulators ◽  
R2r3 Myb

Abstract Background Flavonoid biosynthesis in plants is primarily regulated at the transcriptional level by transcription factors modulating the expression of genes encoding enzymes in the flavonoid pathway. One of the most studied transcription factor complexes involved in this regulation consists of a MYB, bHLH and WD40. However, in Chinese Narcissus (Narcissus tazetta L. var. chinensis), a popular monocot bulb flower, the regulatory mechanism of flavonoid biosynthesis remains unclear. Results In this work, genes related to the regulatory complex, NtbHLH1 and a R2R3-MYB NtMYB6, were cloned from Chinese Narcissus. Phylogenetic analysis indicated that NtbHLH1 belongs to the JAF13 clade of bHLH IIIf subgroup, while NtMYB6 was highly homologous to positive regulators of proanthocyanidin biosynthesis. Both NtbHLH1 and NtMYB6 have highest expression levels in basal plates of Narcissus, where there is an accumulation of proanthocyanidin. Ectopic over expression of NtbHLH1 in tobacco resulted in an increase in anthocyanin accumulation in flowers, and an up-regulation of expression of the endogenous tobacco bHLH AN1 and flavonoid biosynthesis genes. In contrast, the expression level of LAR gene was significantly increased in NtMYB6-transgenic tobacco. Dual luciferase assays showed that co-infiltration of NtbHLH1 and NtMYB6 significantly activated the promoter of Chinese Narcissus DFR gene. Furthermore, a yeast two-hybrid assay confirmed that NtbHLH1 interacts with NtMYB6. Conclusions Our results suggest that NtbHLH1 may function as a regulatory partner by interacting directly with NtMYB6 to enhance proanthocyanidin accumulation in Chinese Narcissus.

scholarly journals The Assessment of IL-21 and IL-22 at the mRNA Level in Tumor Tissue and Protein Concentration in Serum and Peritoneal Fluid in Patients with Ovarian Cancer

2021 ◽  
Vol 10 (14) ◽  
pp. 3058
Author(s):  
Aleksandra Mielczarek-Palacz ◽  
Celina Kruszniewska-Rajs ◽  
Marta Smycz-Kubańska ◽  
Jarosław Strzelczyk ◽  
Wojciech Szanecki ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Peritoneal Fluid ◽  
Tumor Tissue ◽  
Mrna Level ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
First Time ◽  
Ovarian Serous Cancer

The aim of the analysis was for the first time to assess the expression of genes encoding IL-21 and IL-22 at the mRNA level in ovarian tumor specimens and the concentration of these parameters in serum and peritoneal fluid in patients with ovarian serous cancer. The levels of IL-21 and IL-22 transcripts were evaluated with the use of the real-time RT-qPCR. Enzyme-linked immunosorbent assay (ELISA) was used to determine the concentration of proteins. Quantitative analysis of IL-21 gene mRNA in the tumor tissue showed the highest activity in the G1 degree of histopathological differentiation and was higher in G1 compared to the control group. The concentration of IL-21 and IL-22 in the serum and in the peritoneal fluid of women with ovarian cancer varied depending on the degree of histopathological differentiation of the cancer and showed statistical variability compared to controls. The conducted studies have shown that the local and systemic changes in the immune system involving IL-21 and IL-22 indicate the participation of these parameters in the pathogenesis of ovarian cancer, and modulation in the IL-21/IL-22 system may prove useful in the development of new diagnostic and therapeutic strategies used in patients, which require further research.

scholarly journals In vivo transcriptome analysis provides insights into host-dependent expression of virulence factors by Yersinia entomophaga MH96, during infection of Galleria mellonella

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Amber R Paulson ◽  
Maureen O’Callaghan ◽  
Xue-Xian Zhang ◽  
Paul B Rainey ◽  
Mark R H Hurst
Keyword(s):  
Galleria Mellonella ◽  
Functional Enrichment ◽  
Natural Environments ◽  
Insecticidal Toxin ◽  
Heat Stable ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Cell Densities

Abstract The function of microbes can be inferred from knowledge of genes specifically expressed in natural environments. Here, we report the in vivo transcriptome of the entomopathogenic bacterium Yersinia entomophaga MH96, captured during initial, septicemic, and pre-cadaveric stages of intrahemocoelic infection in Galleria mellonella. A total of 1285 genes were significantly upregulated by MH96 during infection; 829 genes responded to in vivo conditions during at least one stage of infection, 289 responded during two stages of infection, and 167 transcripts responded throughout all three stages of infection compared to in vitro conditions at equivalent cell densities. Genes upregulated during the earliest infection stage included components of the insecticidal toxin complex Yen-TC (chi1, chi2, and yenC1), genes for rearrangement hotspot element containing protein yenC3, cytolethal distending toxin cdtAB, and vegetative insecticidal toxin vip2. Genes more highly expressed throughout the infection cycle included the putative heat-stable enterotoxin yenT and three adhesins (usher-chaperone fimbria, filamentous hemagglutinin, and an AidA-like secreted adhesin). Clustering and functional enrichment of gene expression data also revealed expression of genes encoding type III and VI secretion system-associated effectors. Together these data provide insight into the pathobiology of MH96 and serve as an important resource supporting efforts to identify novel insecticidal agents.

scholarly journals Effect of temperature and surfactant on biomass growth and higher-alcohol production during syngas fermentation by Clostridium carboxidivorans P7

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Shaohuang Shen ◽  
Guan Wang ◽  
Ming Zhang ◽  
Yin Tang ◽  
Yang Gu ◽  
...  
Keyword(s):  
Tween 80 ◽  
Biofuel Production ◽  
Effect Of Temperature ◽  
Biomass Growth ◽  
Syngas Fermentation ◽  
Higher Alcohol ◽  
Alcohol Production ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Clostridium Carboxidivorans

Abstract Hexanol–butanol–ethanol fermentation from syngas by Clostridium carboxidivorans P7 is a promising route for biofuel production. However, bacterial agglomeration in the culture of 37 °C severely hampers the accumulation of biomass and products. To investigate the effect of culture temperature on biomass growth and higher-alcohol production, C. carboxidivorans P7 was cultivated at both constant and two-step temperatures in the range from 25 to 37 °C. Meanwhile, Tween-80 and saponin were screened out from eight surfactants to alleviate agglomeration at 37 °C. The results showed that enhanced higher-alcohol production was contributed mainly by the application of two-step temperature culture rather than the addition of anti-agglomeration surfactants. Furthermore, comparative transcriptome revealed that although 37 °C promoted high expression of genes involved in the Wood–Ljungdahl pathway, genes encoding enzymes catalyzing acyl-condensation reactions associated with higher-alcohol production were highly expressed at 25 °C. This study gained greater insight into temperature-effect mechanism on syngas fermentation by C. carboxidivorans P7.

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