Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to investigate the expression of Th1 and Th2 cytokines in the vaginal candidiasis caused by Candida, the fungal vaginitis model was established in female ICR mice by intravaginal inoculation of suspension of C. albicans after the animals were pretreated with estradiol. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect the expression of IL-2, IL-4, IL-10 and TGF-beta1 in the vagina in the mice of different groups at different time points after the beginning of the experiment. The average expression level of IL-2 mRNA in group D (estrogen-treated mice) was significantly higher than that in groups H (estrogen-untreated mice) and I (control group) on the day 2. The average expression level of IL-4 mRNA in group D was significantly higher than that in groups I and H on the day 5. The average expression level of IL-10 mRNA in group D was significantly higher than that in groups H and I from day 7 to 11. The average expression level of TGF-beta1 mRNA in group D was significantly higher than that in groups H and I at all time points. It was concludes that the high-level expression of IL-2 mRNA during early infection was associated with clearance of mucosal C. albicans, and the high-level expression of IL-10 mRNA during late stage of the infection was related to susceptibility to infection. TGF-beta1 may play a predominant role when the virtual absence of changes in other Th-type cytokines during infection.
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PMID:Local Th1/Th2 cytokine expression in experimental murine vaginal candidiasis. 1856 41

Macrophages polarize into functionally distinct subtypes while responding to microenvironmental cues. The identity of proximal transcription factors (TFs) downstream from the polarization signals are known, but their activity is typically transient, failing to explain the long-term, stable epigenomic programs developed. Here, we mapped the early and late epigenomic changes of interleukin-4 (IL-4)-induced alternative macrophage polarization. We identified the TF, early growth response 2 (EGR2), bridging the early transient and late stable gene expression program of polarization. EGR2 is a direct target of IL-4-activated STAT6, having broad action indispensable for 77% of the induced gene signature of alternative polarization, including its autoregulation and a robust, downstream TF cascade involving PPARG. Mechanistically, EGR2 binding results in chromatin opening and the recruitment of chromatin remodelers and RNA polymerase II. Egr2 induction is evolutionarily conserved during alternative polarization of mouse and human macrophages. In the context of tissue resident macrophages, Egr2 expression is most prominent in the lung of a variety of species. Thus, EGR2 is an example of an essential and evolutionarily conserved broad acting factor, linking transient polarization signals to stable epigenomic and transcriptional changes in macrophages.
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PMID:The transcription factor EGR2 is the molecular linchpin connecting STAT6 activation to the late, stable epigenomic program of alternative macrophage polarization. 3306 Jan 36

Interleukin-4 (IL4) is activated as an immune response during infection or tissue injury. Epigenetic programming of maternal high-fat (HF) diet has long-term effects in the offspring. In the present study, we investigated the epigenetic regulation of IL4 in a maternal HF diet model in the liver of adult offspring. Timed-pregnant Sprague-Dawley rats were fed either control or HF diet throughout gestation and lactation. Offspring were placed on a control diet after weaning, generating C/C and HF/C groups. The liver was collected at 12 weeks of age and followed by histological and molecular analysis to investigate the maternal programming effects of IL4 by HF diet. Maternal HF diet significantly induced mRNA expression and protein level of IL4 while promoted hypomethylation of Il4 comparing to the control group. Methylation-selective PCR (MSP) confirmed maternal HF diet increased RNA polymerase II, acetylation of histone H4, and dimethylation of Histone 3 lysine 4 at the +6kb region of Il4. Moreover, rat eosinophil marker, Siglec-F was increased and co-localized with IL4 in the liver. In conclusion, our study indicated that IL4 was increased in liver cells in response to maternal HF diet. This coincides with DNA hypomethylation in combination with chromatin remodeling at the +6 kb of the 3' downstream region, as well as an induced immune cell infiltration, especially eosinophil infiltration, in the liver of offspring.
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PMID:Maternal High Fat Diet Activates Hepatic Interleukin 4 in Rat Male Offspring Accompanied by Increased Eosinophil Infiltration. 3311 58


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