共查询到20条相似文献,搜索用时 15 毫秒
1.
Sung Ji Choi Ik Jae Shin Kang-Hoon Je Eun Kyoung Min Eun Ji Kim Hee-Sun Kim Senyon Choe Dong-Eog Kim Dong Kun Lee 《PloS one》2013,8(3)
Although both glucose deprivation and hypoxia have been reported to promote cascades of biological alterations that lead to induction of inflammatory mediators, we hypothesized that glucose deprivation and hypoxia might show neutral, synergistic or antagonistic effects to each other on gene expression of inflammatory mediators depending on the regulatory components in their promoters. Gene expression of interleukin 6 (IL-6) was analyzed by real-time PCR, ELISA, or Western blot. Effects of glucose deprivation and/or hypoxia on activation of signaling pathways were analyzed by time-dependent phosphorylation patterns of signaling molecules. We demonstrate that hypoxia antagonized the effects of glucose deprivation on induction of IL-6 gene expression in microglia, macrophages, and monocytes. Hypoxia also antagonized thapsigargin-induced IL-6 gene expression. Hypoxia enhanced phosphorylation of Akt, and inhibition of Akt was able to reverse the effects of hypoxia on IL-6 gene expression. However, inhibition of HIF-1/2α did not reverse the effects of hypoxia on IL-6 gene expression. In addition, phosphorylation of p38, but not JNK, was responsible for the effects of glucose deprivation on IL-6 gene expression. 相似文献
2.
Jonah R. Riddell Patricia Maier Stephanie N. Sass Michael T. Moser Barbara A. Foster Sandra O. Gollnick 《PloS one》2012,7(11)
Chronic inflammation leads to the formation of a pro-tumorigenic microenvironment that can promote tumor development, growth and differentiation through augmentation of tumor angiogenesis. Prostate cancer (CaP) risk and prognosis are adversely correlated with a number of inflammatory and angiogenic mediators, including Toll-like receptors (TLRs), NF-κB and vascular endothelial growth factor (VEGF). Peroxiredoxin 1 (Prx1) was recently identified as an endogenous ligand for TLR4 that is secreted from CaP cells and promotes inflammation. Inhibition of Prx1 by CaP cells resulted in reduced expression of VEGF, diminished tumor vasculature and retarded tumor growth. The mechanism by which Prx1 regulates VEGF expression in normoxic conditions was investigated in the current study. Our results show that incubation of mouse vascular endothelial cells with recombinant Prx1 caused increases in VEGF expression that was dependent upon TLR4 and required hypoxia inducible factor-1 (HIF-1) interaction with the VEGF promoter. The induction of VEGF was also dependent upon NF-κB; however, NF-κB interaction with the VEGF promoter was not required for Prx1 induction of VEGF suggesting that NF-κB was acting indirectly to induce VEGF expression. The results presented here show that Prx1 stimulation increased NF-κB interaction with the HIF-1α promoter, leading to enhanced promoter activity and increases in HIF-1α mRNA levels, as well as augmented HIF-1 activity that resulted in VEGF expression. Prx1 induced HIF-1 also promoted NF-κB activity, suggesting the presence of a positive feedback loop that has the potential to perpetuate Prx1 induction of angiogenesis. Strikingly, inhibition of Prx1 expression in CaP was accompanied with reduced expression of HIF-1α. The combined findings of the current study and our previous study suggest that Prx1 interaction with TLR4 promotes CaP growth potentially through chronic activation of tumor angiogenesis. 相似文献
3.
Due to the variant functions that estrogens play in the regulation of reproduction, development of the mammary gland, growth
and differentiation of cells, estrogen receptors and their genes are considered as a candidates for the markers of production
and functional traits in farm animals, including cattle. In the earliest study, a 2853-bp bovine ER gene 5′-region was PCR
amplified and sequenced. Moreover, for the first time, a polymorphism was described within 5′ region of the bovine ERα gene—A/G
transition lying upstream at position 2591 from acceptor splice site +85, possibly within its promoter—which could be recognized
with RFLP-BglI. In other study we are found second polymorphism—A/G transition at position 1213 from acceptor splice site +85, located
in promoter for exon B. We have examined the specific mRNA expression of ERα in various genotypes using real-time RT-PCR.
We used four animals from each genotype group—AG, GG for BglI and AA, AG for SnaBI—to analyse liver ERα expression at the level of Real-time PCR. Liver samples were taken from the 16 young Friesian bulls
of the different ERα genotypes, slaughtered at the local abattoir. As shown by Real-Time PCR, on the livers of animals with
different genotype ERα mRNA for BglI polymorphism we didn’t found variability, but for SnaBI we have found variability between AG and AA genotypes. 相似文献
4.
Gabriella Leung Bj?rn Petri José Luis Reyes Arthur Wang Jordan Iannuzzi Derek M McKay 《Molecular medicine (Cambridge, Mass.)》2015,21(1):924-936
The adoptive transfer of alternatively activated macrophages (AAMs) has proven to attenuate inflammation in multiple mouse models of colitis; however, the effect of cryopreservation on AAMs, the ability of previously frozen AAMs to block dinitrobenzene sulfonic acid (DNBS) (Th1) and oxazolone (Th2) colitis and their migration postinjection remains unknown. Here we have found that while cryopreservation reduced mRNA expression of canonical markers of interleukin (IL)-4–treated macrophages [M(IL-4)], this step did not translate to reduced protein or activity, and the cells retained their capacity to drive the suppression of colitis. The anticolitic effect of M(IL-4) adoptive transfer required neither T or B cell nor peritoneal macrophages in the recipient. After injection into the peritoneal cavity, M(IL-4)s migrated to the spleen, mesenteric lymph nodes and colon of DNBS-treated mice. The chemokines CCL2, CCL4 and CX3CL1 were expressed in the colon during the course of DNBS-induced colitis. The expression of integrin β7 on transferred M(IL-4)s was required for their anticolitic effect, whereas the presence of the chemokine receptors CCR2 and CX3CR1 were dispensable in this model. Collectively, the data show that M(IL-4)s can be cryopreserved M(IL-4)s and subsequently used to suppress colitis in an integrin β7-dependent manner, and we suggest that these proof-of-concept studies may lead to new cellular therapies for human inflammatory bowel disease. 相似文献
5.
Gao Cheng Liu Wei Wang Xiurong Liu Xiangzhen Zhao Shiguang Fu Songbin 《Cellular and molecular neurobiology》2009,29(8):1161-1168
Inappropriate vascular remodeling is thought to be the main cause of restenosis following angioplasty. Migration of vascular
smooth muscle cells (VSMC) into lumina, which is promoted by degradation of the extracellular matrix by matrix metalloproteinases
(MMPs) plays a causal role in pathological vascular remodeling. The aim of the present research is to explore the effects
of a novel cytokine, IL-17, on migration of VSMC and MMP-9 secretion. Carotid artery VSMC was isolated from Sprague–Dawley
rats. Expression of MMP-9 and cell migration induced by IL-17 and its related signal pathway were detected. The results showed
that IL-17-induced migration of VSMC in an MMP-9-dependent manner. IL-17-induced MMP-9 expression was via p38 MAPK and ERK1/2
dependent NF-κB and AP-1 activation. The present results demonstrated that IL-17 may play a role in vascular remodeling and
targeting IL-17 or its specific downstream mediators is a potentially novel therapeutic pathway for attenuating the post-angioplastic
restenosis. 相似文献
6.
CK1δ modulates the transcriptional activity of ERα via AIB1 in an estrogen-dependent manner and regulates ERα–AIB1 interactions 下载免费PDF全文
Georgios Giamas Leandro Castellano Qin Feng Uwe Knippschild Jimmy Jacob Ross S. Thomas R. Charles Coombes Carolyn L. Smith Long R. Jiao Justin Stebbing 《Nucleic acids research》2009,37(9):3110-3123
7.
8.
Concetta Saponaro Andrea Malfettone Girolamo Ranieri Katia Danza Giovanni Simone Angelo Paradiso Anita Mangia 《PloS one》2013,8(1)
Angiogenesis, which plays an important role in tumor growth and progression of breast cancer, is regulated by a balance between pro- and anti-angiogenic factors. Expression of vascular endothelial growth factor (VEGF) is up-regulated during hypoxia by hypoxia-inducible factor-1α (HIF-1α). It is known that there is an interaction between HIF-1α and BRCA1 carrier cancers, but little has been reported about angiogenesis in BRCA1-2 carrier and BRCAX breast cancers. In this study, we investigated the expression of VEGF and HIF-1α and microvessel density (MVD) in 26 BRCA1-2 carriers and 58 BRCAX compared to 77 sporadic breast cancers, by immunohistochemistry. VEGF expression in BRCA1-2 carriers was higher than in BRCAX cancer tissues (p = 0.0001). Furthermore, VEGF expression was higher in both BRCA1-2 carriers and BRCAX than the sporadic group (p<0.0001). VEGF immunoreactivity was correlated with poor tumor grade (p = 0.0074), hormone receptors negativity (p = 0.0206, p = 0.0002 respectively), and MIB-1-labeling index (p = 0.0044) in familial cancers (BRCA1-2 and BRCAX). The percentage of nuclear HIF-1α expression was higher in the BRCA1-2 carriers than in BRCAX cancers (p<0.05), and in all familial than in sporadic tumor tissues (p = 0.0045). A higher MVD was observed in BRCA1-2 carrier than in BRCAX and sporadic cancer tissues (p = 0.002, p = 0.0001 respectively), and in all familial tumors than in sporadic tumors (p = 0.01). MVD was positively related to HIF-1α expression in BRCA1-2 carriers (r = 0.521, p = 0.006), and, in particular, we observed a highly significant correlation in the familial group (r = 0.421, p<0.0001). Our findings suggest that angiogenesis plays a crucial role in BRCA1-2 carrier breast cancers. Prospective studies in larger BRCA1-2 carrier series are needed to improve the best therapeutic strategies for this subgroup of breast cancer patients. 相似文献
9.
Oliveira T. F. Batista P. R. Leal M. A. Campagnaro B. P. Nogueira B. V. Vassallo D. V. Meyrelles S. S. Padilha Alessandra Simão 《Biological trace element research》2019,187(1):163-171
Biological Trace Element Research - Cadmium exposure is related to cardiovascular diseases, including hypertension, atherosclerosis, increased oxidative stress, endothelial dysfunction, and... 相似文献
10.
Serova O. V. Gantsova E. A. Deyev I. E. Petrenko A. G. 《Russian Journal of Bioorganic Chemistry》2022,48(2):321-325
Russian Journal of Bioorganic Chemistry - Neurexins are a family of synaptic adhesion proteins that play a key role in synapse formation and maintenance. Neurexins undergo extensive alternative... 相似文献
11.
Mateusz Opyrchal Jeffrey L. Salisbury Shuya Zhang James McCubrey John Hawse Mattew P. Goetz Gwen A. Lomberk Tufia Haddad Amy Degnim Carol Lange James N. Ingle Evanthia Galanis Antonino B. D'Assoro 《PloS one》2014,9(5)
Development of endocrine resistance during tumor progression represents a major challenge in the management of estrogen receptor alpha (ERα) positive breast tumors and is an area under intense investigation. Although the underlying mechanisms are still poorly understood, many studies point towards the ‘cross-talk’ between ERα and MAPK signaling pathways as a key oncogenic axis responsible for the development of estrogen-independent growth of breast cancer cells that are initially ERα+ and hormone sensitive. In this study we employed a metastatic breast cancer xenograft model harboring constitutive activation of Raf-1 oncogenic signaling to investigate the mechanistic linkage between aberrant MAPK activity and development of endocrine resistance through abrogation of the ERα signaling axis. We demonstrate for the first time the causal role of the Aurora-A mitotic kinase in the development of endocrine resistance through activation of SMAD5 nuclear signaling and down-regulation of ERα expression in initially ERα+ breast cancer cells. This contribution is highly significant for the treatment of endocrine refractory breast carcinomas, because it may lead to the development of novel molecular therapies targeting the Aurora-A/SMAD5 oncogenic axis. We postulate such therapy to result in the selective eradication of endocrine resistant ERαlow/− cancer cells from the bulk tumor with consequent benefits for breast cancer patients. 相似文献
12.
13.
14.
15.
16.
Nectaria X Leandros L Ioannis G Agathocles T 《Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology》2012,28(7):505-508
Estrogens act through binding to estrogen receptor α (ERα) and β (ERβ). Studies in knockout mice have shown that the absence of ERα leads to the polycystic ovary syndrome (PCOS) phenotype. Furthermore, the expression of ERβ gene is lower in follicles derived from women with PCOS compared with healthy women. The aim of this study was to investigate the importance of ERα and ERβ gene polymorphisms in PCOS. A cohort of 180 women with PCOS and 140 healthy controls were recruited, and the PvuII and XbaI polymorphisms of ERα, as well as, the AluI and RsaI polymorphisms of ERβ were genotyped. No difference was found in the distribution of these polymorphisms between patients and healthy controls. However, in PCOS women, carriers of TC and TT genotypes of PvuII polymorphism had lower fasting glucose to insulin ratio compared with carriers of CC genotype (p = 0.029). In addition, the presence of AA genotype of XbaI polymorphism was associated with lower levels of follicle-stimulating hormone (FSH) compared with the presence of AG and GG genotypes (p = 0.03). The association of ERα polymorphisms with insulin resistance indices and FSH levels emphasizes the importance of ERα as a genetic modifier of the PCOS phenotype. 相似文献
17.
Marcela Brissova Rachana Haliyur Diane Saunders Shristi Shrestha Chunhua Dai David M. Blodgett Rita Bottino Martha Campbell-Thompson Radhika Aramandla Gregory Poffenberger Jill Lindner Fong Cheng Pan Matthias G. von Herrath Dale L. Greiner Leonard D. Shultz May Sanyoura Louis H. Philipson Mark Atkinson Alvin C. Powers 《Cell reports》2018,22(10):2667-2676
18.
Ahmed A. Mostafa Dianne Codner Kensuke Hirasawa Yumiko Komatsu Matthew N. Young Viktor Steimle Sheila Drover 《PloS one》2014,9(1)
The coordinate regulation of HLA class II (HLA-II) is controlled by the class II transactivator, CIITA, and is crucial for the development of anti-tumor immunity. HLA-II in breast carcinoma is associated with increased IFN-γ levels, reduced expression of the estrogen receptor (ER) and reduced age at diagnosis. Here, we tested the hypothesis that estradiol (E2) and ERα signaling contribute to the regulation of IFN-γ inducible HLA-II in breast cancer cells. Using a panel of established ER− and ER+ breast cancer cell lines, we showed that E2 attenuated HLA-DR in two ER+ lines (MCF-7 and BT-474), but not in T47D, while it augmented expression in ER− lines, SK-BR-3 and MDA-MB-231. To further study the mechanism(s), we used paired transfectants: ERα+ MC2 (MDA-MB-231 c10A transfected with the wild type ERα gene) and ERα− VC5 (MDA-MB-231 c10A transfected with the empty vector), treated or not with E2 and IFN-γ. HLA-II and CIITA were severely reduced in MC2 compared to VC5 and were further exacerbated by E2 treatment. Reduced expression occurred at the level of the IFN-γ inducible CIITA promoter IV. The anti-estrogen ICI 182,780 and gene silencing with ESR1 siRNA reversed the E2 inhibitory effects, signifying an antagonistic role for activated ERα on CIITA pIV activity. Moreover, STAT1 signaling, necessary for CIITA pIV activation, and selected STAT1 regulated genes were variably downregulated by E2 in transfected and endogenous ERα positive breast cancer cells, whereas STAT1 signaling was noticeably augmented in ERα− breast cancer cells. Collectively, these results imply immune escape mechanisms in ERα+ breast cancer may be facilitated through an ERα suppressive mechanism on IFN-γ signaling. 相似文献
19.
20.