Glucocorticoids (GC) are used as first line therapies for generalized suppression of inflammation (e.g. allergies or autoimmune diseases), but their long-term use is limited by severe side effects. Our previous work has revealed that GC induced a stable anti-inflammatory phenotype in monocytes, the glucocorticoid-stimulated monocytes (GCsM) that we now exploited for targeted GC-mediated therapeutic effects.
Immune suppression via glucocorticoid-stimulated monocytes: a novel mechanism to cope with inflammation.
Specimen part, Treatment
View SamplesBackground and Aims: In the interleukin-10-deficient (Il10-/-) mouse model of IBD, 10 quantitative trait loci (QTL) have been shown to be associated with colitis susceptibility by linkage analyses on experimental crosses of highly susceptible C3H/HeJBir (C3Bir)-Il10-/- and partially resistant C57BL/6J (B6)-Il10-/- mice. The strongest locus (C3Bir-derived cytokine deficiency-induced colitis susceptibility [Cdcs]1 on Chromosome [Chr] 3) controlled multiple colitogenic subphenotypes and contributed the vast majority to the phenotypic variance in cecum and colon. This was demonstrated by interval-specific Chr 3 congenic mice wherein defined regions of Cdcs1 from C3Bir or B6 were bred into the IL-10-deficient reciprocal background and altered the susceptible or resistant phenotype. Furthermore, this locus likely acts by inducing innate hypo- and adaptive hyperresponsiveness, associated with impaired NFB responses of macrophages. The aim of the present study was to dissect the complexity of Cdcs1 by further development and characterization of reciprocal Cdcs1 congenic strains and to identify potential candidate genes in the congenic interval. Material and Methods: In total, 15 reciprocal congenic strains were generated from Il10-/- mice of either C3H/HeJBir or C57BL/6J backgrounds by 10 cycles of backcrossing. Colitis activity was monitored by histological grading. Candidate genes were identified by fine mapping of congenic intervals, sequencing, microarray analysis and a high-throughput real-time RT-PCR approach using bone marrow-derived macrophages. Results: Within the originally identified Cdcs1-interval, three independent regions were detected that likely contain susceptibility-determining genetic factors (Cdcs1.1, Cdcs1.2, and Cdcs1.3). Combining results of candidate gene approaches revealed Fcgr1, Cnn3, Larp7, and Alpk1 as highly attractive candidate genes with polymorphisms in coding or regulatory regions and expression differences between susceptible and resistant mouse strains. Conclusions: Subcongenic analysis of the major susceptibility locus Cdcs1 on mouse chromosome 3 revealed a complex genetic structure. Candidate gene approaches revealed attractive genes within the identified regions with homologs that are located in human susceptibility regions for IBD.
Cdcs1 a major colitis susceptibility locus in mice; subcongenic analysis reveals genetic complexity.
Sex, Specimen part
View SamplesSerum response factor (SRF) is a transcription factor that binds to the serum response element (SRE) of genes that are expressed in response to mitogens. SRF plays essential roles in muscle and nervous system development; however, little is known about the role of SRF during liver growth and function. To examine the function of SRF in the liver, we generated mice in which the Srf gene was specifically disrupted in hepatocytes. The survival of mice lacking hepatic SRF activity was lower than that of control mice; moreover, surviving mutant mice were smaller and had lower blood glucose and triglyceride levels compared with control mice. Srf-deficient livers were also smaller than control livers, hepatocyte morphology was abnormal, and liver-cell proliferation and viability was compromised. Gene array and quantitative RT-PCR analysis of SRF depleted livers revealed a reduction in mRNAs encoding components of the growth hormone/IGF1 pathway, cyclins, several metabolic regulators, and cytochrome p450 enzymes. Conclusion: SRF is essential for hepatocyte proliferation and survival, liver function, and control of postnatal body growth by regulating hepatocyte gene expression.
Hepatocyte expression of serum response factor is essential for liver function, hepatocyte proliferation and survival, and postnatal body growth in mice.
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View SamplesThe xylose fermentation capability of an industrainl Saccharomyces cerevisiae strain was enhanced by adaptive evolution. Eight homozygots were generated by tetrads dissection.
Comparative transcriptomes reveal novel evolutionary strategies adopted by Saccharomyces cerevisiae with improved xylose utilization capability.
Genetic information
View SamplesThe xylose fermentation capability of an industrainl Saccharomyces cerevisiae strain was enhanced by adaptive evolution. Eight homozygots were generated by tetrads dissection.
Comparative transcriptomes reveal novel evolutionary strategies adopted by Saccharomyces cerevisiae with improved xylose utilization capability.
Genetic information
View SamplesThe xylose fermentation capability of an industrainl Saccharomyces cerevisiae strain was enhanced by adaptive evolution. Eight homozygots were generated by tetrads dissection.
Comparative transcriptomes reveal novel evolutionary strategies adopted by Saccharomyces cerevisiae with improved xylose utilization capability.
Genetic information
View SamplesThe xylose fermentation capability of an industrainl Saccharomyces cerevisiae strain was enhanced by adaptive evolution. Eight homozygots were generated by tetrads dissection.
Comparative transcriptomes reveal novel evolutionary strategies adopted by Saccharomyces cerevisiae with improved xylose utilization capability.
Genetic information
View SamplesThe xylose fermentation capability of an industrainl Saccharomyces cerevisiae strain was enhanced by adaptive evolution. Eight homozygots were generated by tetrads dissection.
Comparative transcriptomes reveal novel evolutionary strategies adopted by Saccharomyces cerevisiae with improved xylose utilization capability.
Genetic information
View SamplesThe xylose fermentation capability of an industrainl Saccharomyces cerevisiae strain was enhanced by adaptive evolution. Eight homozygots were generated by tetrads dissection.
Comparative transcriptomes reveal novel evolutionary strategies adopted by Saccharomyces cerevisiae with improved xylose utilization capability.
Genetic information
View SamplesThe xylose fermentation capability of an industrainl Saccharomyces cerevisiae strain was enhanced by adaptive evolution. Eight homozygots were generated by tetrads dissection.
Comparative transcriptomes reveal novel evolutionary strategies adopted by Saccharomyces cerevisiae with improved xylose utilization capability.
Genetic information
View Samples