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Hui-Qun Wang

Publications and source records attributed to Hui-Qun Wang.

10 recordsLinked to original sources
PubMed2006

Progesterone-induced sphingosine kinase-1 expression in the rat uterus during pregnancy and signaling consequences.

Sphingosine 1-phosphate (Sph-1-P), a product of sphingomyelin metabolism, can act via a family of cognate G protein-coupled receptors or as an intracellular second messenger for agonists acting through their membrane receptors. In view of the general growth promoting and developmental effects of Sph-1-P on target cells, we hypothesized that it plays a role in adaptation of the uterus to pregnancy. We analyzed its potential role and that of the related lysophospholipid lysophosphatidic acid in the pregnant rat uterus by examining changes in mRNA levels of cognate receptors and enzymes involved in their turnover. Of these, only sphingosine kinase-1 (SphK1) was markedly changed ( approximately 30-fold increase), being localized in the glandular epithelium, vasculature, and the myometrium. Uterine SphK1 mRNA and protein levels paralleled those of serum progesterone, and treatment with progesterone or an antagonist elevated or reduced SphK1 mRNA expression, respectively. Progesterone also increased SphK1 mRNA steady-state levels in a rat myometrial/leiomyoma cell line (ELT3). Overexpressing human SphK1 in these cells resulted in increased levels of the cell cycle regulator cyclin D1 and increased myosin light-chain phosphorylation. Ectopic expression of SphK1 also resulted in increased proliferation rates, possibly in conjunction with increased cyclin D1 expression. These studies suggest that the uterine expression of SphK1 mediates processes involved in growth and differentiation of uterine tissues during pregnancy.

Animals↗
PubMed2006

Circulating calcitonin gene-related peptide and its placental origins in normotensive and preeclamptic pregnancies.

OBJECTIVE: The present study was designed to determine plasma calcitonin gene-related peptide concentration in both maternal and fetal circulations in normotensive and pre-eclamptic pregnancies and investigate whether placenta is 1 of its origins. STUDY DESIGN: Maternal blood, cord blood, and villous tissue were collected from women in normotensive pregnancies and complicated with pre-eclampsia. Calcitonin gene-related peptide concentrations were determined by radioimmunoassay. Cellular localizations of calcitonin gene-related peptide messenger ribonucleic acid and protein expressions in placental villi were determined by in situ hybridization and immunohistochemistry. RESULTS: The following results were reached: (1) maternal plasma calcitonin gene-related peptide concentrations increased with advancing gestation but fell after delivery; (2) both maternal and cord plasma calcitonin gene-related peptide concentrations were positively correlated with the infant birth weights; (3) compared with normotensive pregnancies, calcitonin gene-related peptide levels in both maternal and cord plasma decreased in pregnancies with pre-eclampsia; (4) in normotensive pregnancies, the plasma calcitonin gene-related peptide of the umbilical vein was higher than the umbilical artery, but no significant differences between vein and artery in pre-eclampsia; (5) calcitonin gene-related peptide messenger ribonucleic acid and protein were expressed by syncytiotrophoblast cells and villous vascular endothelial cells in normotensive pregnancies, but only weak or absent staining was observed in pre-eclamptic placentas; and (6) calcitonin gene-related peptide is secreted by villous tissue in explant culture in a time-dependent manner, but less calcitonin gene-related peptide was produced by villous tissues from patients with pre-eclampsia. CONCLUSION: Calcitonin gene-related peptide may play potential roles in maternal hemodynamic adaptation and fetal growth. Decreased circulating calcitonin gene-related peptide levels may be involved in maternal-fetal pathophysiology of pre-eclampsia. It is novel that placenta villous tissues might be one of the potential sources of calcitonin gene-related peptide during pregnancy.

Adult↗
PubMed2006

Estrogenic regulation of host immunity against an estrogen receptor-negative human breast cancer.

PURPOSE: The risk of developing breast cancer is positively correlated with exposure to increased levels of estrogen and/or an increased duration of estrogen exposure. Many different mechanisms have been proposed to explain the association of estrogens with breast cancer risk; however, the well-documented immune modulatory properties of estrogen have received little attention. In part, this is due to a lack of suitable models for studying this relationship. EXPERIMENTAL DESIGN: We have developed an animal model using estrogen receptor (ER)-negative human breast cancer cell line, MDA-MB-468, xenografted into severe combined immunodeficient (SCID) mice. We also generated the ER-alpha knockout (ER-alphaKO) mice on the SCID background and then tested the ability of 17beta-estradiol to stimulate growth of xenografted ER-negative human breast cancer tumors in wild-type and ER-alphaKO SCID mice. We quantified vascularization of tumors, macrophage recruitment to the tumor site by immunocytochemistry, and inflammatory cytokine production. RESULTS: We show that estrogen treatment of C57BL/6/SCID mice promotes the growth of xenografted ER-negative tumors in wild-type mice and this estrogen-induced tumor growth is abrogated in ER-alphaKO mice. Tumor neovascularization of estrogen-treated mice was unchanged versus control; however, estrogen treatment of the C57BL/6/SCID host suppressed macrophage recruitment to and inflammatory cytokine production at the tumor site. CONCLUSIONS: These data are consistent with estrogen modulation of the inflammatory response as a contributing factor in estrogen-stimulated growth of an ER-negative tumor. This effect on the host innate immune response was mediated by ER-alpha.

Animals↗
PubMed2006

An intradermal environment promotes a protective type-1 response against lethal systemic monocytotropic ehrlichial infection.

Immune responses against monocytotropic ehrlichiosis during infection with a strain of Ehrlichia from Ixodes ovatus (IOE) were evaluated using a model that closely reproduces the pathology and immunity associated with tick-transmitted human monocytotropic ehrlichiosis. C57BL/6 mice were inoculated intradermally or intraperitoneally with high-dose highly virulent IOE or intraperitoneally with mildly virulent Ehrlichia muris. Intradermal (i.d.) infection with IOE established mild, self-limited disease associated with minimal hepatic apoptosis, and all mice survived past 30 days. Intraperitoneal (i.p.) infection with IOE resulted in acute, severe toxic shock-like syndrome and severe multifocal hepatic apoptosis and necrosis, and all mice succumbed to disease. Compared to i.p. infection with IOE, intradermally infected mice had a 100- to 1,000-fold lower bacterial load in the spleen with limited dissemination. Compared to mice infected intraperitoneally with IOE, i.d. infection stimulated a stronger protective type-1 cell-mediated response on day 7 of infection, characterized by increased percentages of both CD4+ and CD8+ splenic T cells, generation of a greater number of IOE-specific, gamma interferon-producing CD4+ Th1 cells, and higher levels of tumor necrosis factor (TNF-alpha) in the spleen but lower concentrations of serum TNF-alpha and interleukin-10. These data suggest that under the conditions of natural route of challenge (i.e., i.d. inoculation), the immune response has the capacity to confer complete protection against monocytotropic ehrlichiosis, which is associated with a strong cell-mediated type-1 response and decreased systemic production of pro- and anti-inflammatory cytokines.

Animals↗
PubMed2005

Pyelonephritic Escherichia coli expressing P fimbriae decrease immune response of the mouse kidney.

P fimbriae are proteinaceous appendages on the surface of Escherichia coli bacteria that mediate adherence to uroepithelial cells. E. coli that express P fimbriae account for the majority of ascending urinary tract infections in women with normal urinary tracts. The hypothesis that P fimbriae on uropathic E. coli attach to renal epithelia and may regulate the immune response to establish infection was investigated. The polymeric Ig receptor (pIgR), produced by renal epithelia, transports IgA into the urinary space. Kidney pIgR and urine IgA levels were analyzed in a mouse model of ascending pyelonephritis, using E. coli with (P+) and without (P-) P fimbriae, to determine whether P(+) E. coli regulate epithelial pIgR expression and IgA transport into the urine. (P+) E. coli establish infection and persist to a greater amount than P(-) E. coli. P(+)-infected mice downregulate pIgR mRNA and protein levels compared with P(-)-infected or PBS controls at > or =48 h. The decrease in pIgR was associated with decreased urinary IgA levels in the P(+)-infected group at 48 h. pIgR mRNA and protein also decline in P(+) E. coli-infected LPS-hyporesponsive mice. These studies identify a novel virulence mechanism of E. coli that express P fimbriae. It is proposed that P fimbriae decrease pIgR expression in the kidney and consequently decrease IgA transport into the urinary space. This may explain, in part, how E. coli that bear P fimbriae exploit the immune system of human hosts to establish ascending pyelonephritis.

Animals↗
PubMed2005

Effect of chronic hyperghrelinemia on ingestive action of ghrelin.

The stomach hormone ghrelin is the endogenous ligand for the growth hormone secretagogue receptor (GHS-R). Systemic administration of ghrelin will cause elevations in growth hormone (GH) secretion, food intake, adiposity, and body growth. Ghrelin also affects insulin secretion, gastric acid secretion, and gastric motility. Several reports indicate that repeated or continuous activation of GHS-R by exogenous GHSs or ghrelin results in a diminished GH secretory response. The purpose of this study was to examine the extent to which the acute stimulation of food intake by exogenous ghrelin is altered by chronic hyperghrelinemia in transgenic mice that overexpress the human ghrelin gene. The present findings show that the orexigenic action of exogenous ghrelin is not diminished by a chronic hyperghrelinemia and indicate that the food ingestive pathway of the GHS-R is not susceptible to desensitization. In contrast, the epididymal fat pad growth response, like the GH response, to exogenous ghrelin is blunted in ghrelin transgenic mice with chronic hyperghrelinemia.

Animals↗
PubMed2005

Vaccination with purified Dr Fimbriae reduces mortality associated with chronic urinary tract infection due to Escherichia coli bearing Dr adhesin.

The vaccination of C3H/HeJ mice with Escherichia coli Dr fimbrial antigen reduced mortality associated with an experimental urinary tract infection due to a homologous strain bearing Dr adhesin. Immune sera with high titers of anti-Dr antibody inhibited bacterial binding to bladders and kidneys but did not affect the rate of renal colonization.

Adhesins, Escherichia coli↗
PubMed2004

Molecular characterization of an inward rectifier channel (IKir) found in avian vestibular hair cells: cloning and expression of pKir2.1.

A fast inwardly rectifying current has been observed in some of the sensory cells (hair cells) of the inner ear of several species. While the current was presumed to be an IKir current, contradictory evidence existed as to whether the cloned channel actually belonged to the Kir2.0 subfamily of potassium inward rectifiers. In this paper, we report for the first time converging evidence from electrophysiological, biochemical, immunohistochemical, and genetic studies that show that the Kir2.1 channel carries the fast inwardly rectifying currents found in pigeon vestibular hair cells. Following cytoplasm extraction from single type II and multiple pigeon vestibular hair cells, mRNA was reverse transcribed, amplified, and sequenced. The open reading frame (ORF), consisting of a 1,284-bp nucleotide sequence, showed 94, 85, and 83% identity with Kir2.1 subunit sequences from chick lens, Kir2 sequences from human heart, and a mouse macrophage cell line, respectively. Phylogenetic analyses revealed that pKir2.1 formed an immediate node with hKir2.1 but not with hKir2.2-2.4. Hair cells (type I and type II) and supporting cells in the sensory epithelium reacted positively with a Kir2.1 antibody. The whole cell current recorded in oocytes and CHO cells, transfected with pigeon hair cell Kir2.1 (pKir2.1), demonstrated blockage by Ba2+ and sensitivity to changing K+ concentration. The mean single-channel linear slope conductance in transfected CHO cells was 29 pS. The open dwell time was long (approximately 300 ms at -100 mV), and the closed dwell time was short (approximately 34 ms at -100 mV). Multistates ranging from 3-6 were noted in some single-channel responses. All of the above features have been described for other Kir2.1 channels. Current clamp studies of native pigeon vestibular hair cells illustrated possible physiological roles of the channel and showed that blockage of the channel by Ba2+ depolarized the resting membrane potential by approximately 30 mV. Negative currents hyperpolarized the membrane approximately 20 mV before block but approximately 60 mV following block. RT-PCR studies revealed that the pKir2.1 channels found in pigeon vestibular hair cells were also present in pigeon vestibular nerve, vestibular ganglion, lens, neck muscle, brain (brain stem, cerebellum and optic tectum), liver, and heart.

Amino Acid Sequence↗
PubMed2004

The hamster as an animal model for eastern equine encephalitis--and its use in studies of virus entrance into the brain.

Eastern equine encephalitis virus (EEEV) produces the most severe human arboviral diseases in the United States, with mortality rates of 30%-70%. Vasculitis associated with microhemorrhages in the brain dominates the pathological picture in fatal human eastern equine encephalitis, and neuronal cell death is detectable during the late stage of the disease. We describe use of the golden hamster to study EEEV-induced acute vasculitis and encephalitis. In hamsters, EEEV replicates in visceral organs, produces viremia, and penetrates the brain. The pathological manifestations and antigen distribution in the brain of a hamster are similar to those described in human cases of EEEV.

Animals↗