Toll-like receptors(TLRs) recognize microbial pathogens and trigger immune response, buttheir regulation by neuropeptidevasoactive intestinal peptide(VIP) in weaned piglet infectedby enterotoxigenic Escherichia coli(E...
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Toll-like receptors(TLRs) recognize microbial pathogens and trigger immune response, buttheir regulation by neuropeptidevasoactive intestinal peptide(VIP) in weaned piglet infectedby enterotoxigenic Escherichia coli(ETEC) K88 remains unexplored. Therefore, thestudy was conducted to investigate its role using a model of early weaned piglets infectedby ETEC K88. Male Duroc×Landrace×Yorkshire piglets(n=24) were randomly divided intocontrol, ETEC K88, VIP, and ETEC K88+VIP groups. On the first three days, ETEC K88 andETEC K88+VIP groups were orally administrated with ETEC K88, other two groups were givensterile medium. Then each piglet from VIP and ETEC K88+VIP group received 10 nmolVIP intraperitoneally(i.p.) once daily, on day four and six. On the seventh day, the pigletswere sacrificed. The results indicated that administration of VIP improved the growth performance,reduced diarrhea incidence of ETEC K88 challenged pigs, and mitigated the histopathologicalchanges of intestine. Serum levels of IL-2, IL-6, IL-12p40, IFN-γ and TNF-αin the ETEC K88 + VIP group were significantly reduced compared with those in the ETECgroup. VIP significantly increased IL-4, IL-10, TGF-β and S-IgA production compared withthe ETEC K88 group. Besides, VIP could inhibit the expression of TLR2, TLR4, MyD88, NF-κBp65 and the phosphorylation of IκB-α, p-ERK, p-JNK, and p-38 induced by ETEC ***, VIP could upregulate the expression of occludin in the ileum mucosa comparedwith the ETEC K88 group. Colon and caecum content bacterial richness and diversity werelower for pigs in the ETEC group than the unchallenged groups.. These results demonstratethat VIP is beneficial for the maturation of the intestinal mucosal immune system and elicitedlocal immunomodulatory activities. The TLR2/4-MyD88 mediated NF-κB and MAPKsignaling pathway may be critical to the mechanism underlying the modulatory effect ofVIP on intestinal mucosal immune function and bacterial community.
Acyl-coenzyme A:cholesterol acyltransferase(ACAT) catalyzes the formation of cholesteryl ester from cholesterol and longchain fatty acyl-coenzyme A, and is a key enzyme in the cellular cholesterol metabolism. So far, ...
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Acyl-coenzyme A:cholesterol acyltransferase(ACAT) catalyzes the formation of cholesteryl ester from cholesterol and longchain fatty acyl-coenzyme A, and is a key enzyme in the cellular cholesterol metabolism. So far, two human ACAT1 isoforms(50- and 56-kD) have been identified. We have previously reported that the expression of 50-kD isoform and chromosome 1-derived ACAT1 mRNA can be up-regulated by the inflammatory factor interferon-γ(IFN-γ) or tumor necrosis factor-α(TNF-α) specifically in human monocytic cells. Recently, it has been uncovered that human ACAT1 56-kD isoform is translated from a multi-chimeric mRNA by a novel exo-endo trans-splicing between an asAmp transcript and the ACAT1 4.3-kb chimeric mRNA with an optional long 5'-UTR, which contains chromosome 7-derived lncRNA ACAT1C7 sequence to decay its linked ACAT1 mRNA. Based on those progresses, this work focuses on the effect of the cellular cholesterol on the expression of human ACAT1 56-kD isoform. First of all, it is interestingly observed that human ACAT1 56-kD isoform is induced in monocytic cell line THP-1 by the treatment of IFN-γ plus ATRA or TNF-α together with the high dose of the oxidized low-density lipoprotein(oxLDL), which leads to the high-level cholesterol in cells. Next, when the high dose of mevalonate is used to boost cellular cholesterol level, human ACAT1 56-kD isoform is also increased in different non-monocytic cell lines. Besides, we have transfected cells with plasmid pVk-ACAT1-C7, which can highly express chromosome 7-derived lncRNA ACAT1C7, and then observed that human ACAT1 56-kD isoform is evidently increased. Furthermore, by using actinomycin D to inhibit the mRNA transcription, the RT-qPCR results indicate that the high-level cellular cholesterol can promote the decay of chromosome 1-derived ACAT1 mRNA transcribed by polymerase II. Accordingly, we speculate that the high-level cellular cholesterol may promote the polymerase IⅡtranscription of chromosome 7-derived lncRNA A
Objective: Gene activation in eukaryotes requires coordinated role of specific cell signals,transcription factor activation, chromatin modications, and chromatin remodeling. KLF4(Kruppel-like factor 4), which can be a...
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Objective: Gene activation in eukaryotes requires coordinated role of specific cell signals,transcription factor activation, chromatin modications, and chromatin remodeling. KLF4(Kruppel-like factor 4), which can be acetylated by p300, is closely involved in vascularsmooth muscle cell(VSMC) differentiation gene induced by transforming growth factor β***, a direct relationship between transcription activation by KLF4 and histone acetylation remains unknown. In this study, we report an alternative activation mechanism ofp21 that involves acetylation of KLF4 by p300 and H3 acetylation by KLF4-recruited *** and Results: In the present study, TGF-β1 increased KLF4, H3 and H4 acetylation in a dose- and time-dependent manner. KLF4 over expression further increased TGFβ1-induced H3 acetylation, knockdown of KLF4 by KLF4-siRNA abrogated the inducing effect of TGFβ1 on H3 acetylation. ChIP analysis showed that H3 acetylation was highly concentrated between-225 bp and 57 bp of the p21 promoter in VSMCs infected with pAd-GFPKLF4,but the occupancy of p300 at the p21 promoter appeared concentrated in-645 bp/-397 bp and-225 bp/57 bp of p21 promoter regions which contain both smad site and TCEsite. ChIP results showed that KLF4, p300 and H3 acetylation all exhibited the greatest increase in-225 bp/57 bp of p21 promoter region when VSMCs were infected with pAd-GFP-KLF4. These results suggest that KLF4 is essential for H3 acetylation and recruition ofp300 to specific sites of p21 promoter. Coimmunoprecipitation(Co-IP), GST pulldown, and ChIP analysis showed that on activation of TGFβ1 signaling, KLF4-p300 interaction increased,PTEN was dissociated from the KLF4-PTEN complex through P38 and AKT mediated PTEN phosphorylation. Immunoprecipitation assay indicated that p300 could acetylate KLF4, meanwhile PTEN could dephosphorylate KLF4. The underlying mechanism of p300, PTEN and KLF4 posttranslational activation was explored by western blot, the results indicated that p300
Breast cancer is a major cause of mortality among women. Paclitaxel is commonly used forchemotherapy of breast cancer, yet its efficacy is limited by chemoresistance. Generally,drug resistance is associated with acqui...
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Breast cancer is a major cause of mortality among women. Paclitaxel is commonly used forchemotherapy of breast cancer, yet its efficacy is limited by chemoresistance. Generally,drug resistance is associated with acquisition of the epithelialmesenchymal transition(EMT) in cancer. Targeting EMT could be a novel therapeutic strategy for treatment ofbreast cancer. The evidence of microRNAs involvement in cancer drug resistance has beenemerging recently. MicroRNAs are master regulators of gene expression in many biologicaland pathological processes, including mammary gland development and breast *** of these microRNAs have been shown to control cellular plasticity through the suppressionof EMT-inducers or to influence cellular phenotype through the suppression ofgenes involved in defining the epithelial and mesenchymal cell states. To investigate therole of miR-125 b in the development of resistance to paclitaxel as well as accompanyingEMT-like properties, we established a paclitaxel-resistant model by continually exposingMCF-7 and SKBR-3 breast cancer cells to paclitaxel. Using the paclitaxel-resistant MCF-7/PTX and SKBR-3/PTX cell lines, we examined the cellular morphology, molecularchanges, migration and proliferation consistent with the EMT. Down-regulated miR-125 bwas observed in human breast cancer cells resistant to MCF-7/PTX and SKBR-3/PTX ascompared to the parental MCF-7 and SKBR-3 cells. Up-regulation of miR-125 b with transfectionof miR-125 b mimics in MCF-7/PTX and SKBR-3/PTX was sufficient to sensitizeMCF-7/PR and SKBR-3/PR cells to paclitaxel and partly reversed EMT. A combination ofmRNA profiling, bioinformatics analysis and experimental validation identified SEMA4 C asa direct target of miR-125 b. The functional interaction between miR-125 b and the targetgene, SEMA4 C, was examined using the luciferase reporter assay and western ***-125 b negatively regulated SEMA4 C expression by binding to the 3'-untranslated regionof SEMA4 C. Silencin
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