Abstract:
:Pathogenic inflammation mediated by overactive type 1 helper T cell (Th1) responses could exacerbate and perpetuate Crohn's disease. Programmed death (PD)-1 and its ligand PD-L1 pathway could be upregulated to suppress inflammation. We wondered why this pathway is ineffective at suppressing pathogenic Th1 inflammation in Crohn's disease patients. Here, we found that overexpression of T-bet via transfection significantly reduced the expression of PD-1. PD-L1 was capable of suppression proinflammatory CD4+ T cells, but T-bet transfection significantly reduced the susceptibility of CD4+ T cells toward PD-L1-mediated suppression, evidenced by the observations that at low PD-L1 concentration T-bet transfected and mock transfected CD4+ T cells presented comparable IL-2 production, but at high PD-L1 concentration, T-bet transfected CD4+ T cells presented significantly higher IL-2 than mock transfected CD4+ T cells. PD-L1 could significantly reduce the survival of CD4+ T cells from Crohn's disease patients, but interestingly, in the absence of PD-L1, the survival was better in mock transfected CD4+ T cells, while in the presence of PD-L1, the survival was better in T-bet transfected CD4+ T cells. Crohn's disease patients with greater severity presented higher T-bet expression and lower PD-1 expression in CD4+ T cells, demonstrating an association between T-bet expression and disease progression. We also discovered that stimulation with bacterial antigens could upregulate the expression of T-bet. Together, this study demonstrated that T-bet overexpression could interfere with PD-1/PD-L1-mediated suppression of CD4+ T cell inflammation and survival, and potentially contributed to the development and persistence of Crohn's disease.
journal_name
Clin Exp Pharmacol Physioljournal_title
Clinical and experimental pharmacology & physiologyauthors
Ma F,Zhao M,Song Z,Wang Zdoi
10.1111/1440-1681.13127subject
Has Abstractpub_date
2019-09-01 00:00:00pages
798-805issue
9eissn
0305-1870issn
1440-1681journal_volume
46pub_type
杂志文章abstract::1. Contraction assays and patch clamp methods were used to determine the role of K+ channels in the regulation of contractile tone of human mesangial cells (MC) in culture. 2. MC contraction was induced by vasoconstrictor agents, such as angiotensin II (AngII; 100 nmol/L) and glybenclamide (Glyb), but not by iberiotox...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1996.tb03066.x
更新日期:1996-01-01 00:00:00
abstract::1. Endothelin mediates its effects in a variety of renal cells via a multiplicity of intracellular signalling pathways. 2. Stimulation of phosphatidylinositol-specific phospholipase C (PI-PLC), resulting in the activation of inositol trisphosphate and diacylglycerol, can be detected even at picomolar concentrations of...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.1996.tb02833.x
更新日期:1996-04-01 00:00:00
abstract::1. L-Type Ca2+ channels play important roles in cardiac excitation and conduction. The present study used the whole-cell patch-clamp technique to investigate properties of Ca2+ channels in guinea-pig isolated ventricular myocytes. The effects of internal application of the proteolytic enzymes trypsin and carboxypeptid...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.1999.02999.x
更新日期:1999-02-01 00:00:00
abstract::1. The aim of this study was to assess the vagal and sympathetic nerve contribution to the relationship between mean arterial pressure (MAP) and heart rate (HR) at 6, 9, 14 and 20 weeks of age in conscious Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) with methoxamine- and nitroprusside-induced steady-s...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1988.tb01075.x
更新日期:1988-04-01 00:00:00
abstract::1. Indices quantifying blood pressure (BP) and heart rate (HR) variability have been recently developed and may be used to assess the contribution of the autonomic nervous system to cardiovascular fluctuations. 2. Cardiovascular variables were measured in eight conscious mice equipped with a BP telemetric device. Each...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2008.04895.x
更新日期:2008-04-01 00:00:00
abstract::1. The aim of the present study was to investigate the effects of hypoxia on energy metabolism and contraction of rat urinary bladder smooth muscle, thereby gaining insight into the capacity of this smooth muscle to maintain contractile function when rendered hypoxic. 2. Isometric force, oxygen consumption, lactate pr...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2003.03882.x
更新日期:2003-08-01 00:00:00
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journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.2009.05213.x
更新日期:2009-12-01 00:00:00
abstract::1. Angiotensin (Ang)II is involved in responses to hypovolaemia, such as sodium appetite and increase in blood pressure. Target areas subserving these responses for AngII include the cardiovascular system in the periphery and the circumventricular organs in the brain. 2. Conflicting data have been reported for the rol...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1046/j.1440-1681.2000.03262.x
更新日期:2000-05-01 00:00:00
abstract::1. The concentrations of gamma-amino butyric acid (GABA) and glutamate were measured in the brains of chickens which were treated with furazolidone (FZ) or nitrofurazone (NF) at oral doses of 12.5, 25 or 50 mg/kg for 5 days. 2. At the end of the treatment, the birds lost about 9% of their bodyweight when on the small ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1989.tb01572.x
更新日期:1989-05-01 00:00:00
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journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2004.04069.x
更新日期:2004-10-01 00:00:00
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journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2006.04492.x
更新日期:2006-11-01 00:00:00
abstract::1. Calcified arteriosclerotic lesions have been recognized early in life as abnormalities in coronary arteries. 2. We examined coronary arterial plaques as an undecalcified tissue and revealed widespread mineralization within the plaque. Non-collagenous proteins that regulate calcification, such as osteopontin, have b...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1996.tb02609.x
更新日期:1996-03-01 00:00:00
abstract::1. Nitric oxide (NO), or peroxynitrite, is known to inhibit haemoproteins, including cytochrome P450 mono-oxygenases. The present study explores the functional correlates of the inhibition by NO of renal epoxygenase on the vascular responses to arachidonic acid (AA) in the perfused kidney. 2. Control kidneys produce m...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2002.03762.x
更新日期:2002-11-01 00:00:00
abstract::1. Activation of peripheral chemoreceptors with KCN in the working heart-brainstem preparation from young male Wistar rats (70-90 g) increases phrenic (PNA; +105 +/- 18%) and thoracic (tSNA; +44 +/- 6%) sympathetic nerve activity compared with baseline and reduces heart rate (HR; from 377 +/- 27 to 83 +/- 6 b.p.m.). 2...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2005.04213.x
更新日期:2005-05-01 00:00:00
abstract::1. Renin is highly expressed in submandibular gland (SMG) of mouse, which has two genes, Ren-1d and Ren-2d, but not at all in rat SMG. Differences in nuclear protein binding to renin promoter DNA were, therefore, explored. 2. Rat -169 to +23 renin DNA formed complexes with both mouse and rat extract, whereas a corresp...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1993.tb01684.x
更新日期:1993-05-01 00:00:00
abstract::1. The effects of bromocriptine and indomethacin on prolactin-induced pseudopregnancy were studied in pituitary grafted rats. 2.Administration of bromocriptine (a prolactin suppressant drug) at a total dose of 3 mg/kg body weight, given in 3 divided doses on day 5 of pseudopregnancy, effectively terminated it within 3...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1980.tb00079.x
更新日期:1980-05-01 00:00:00
abstract::1. Cardiovascular events and outcome in septic shock may be predicted by monitoring the fall in intramural pH (pHi), as an index of splanchnic perfusion and mucosal ischaemia. In the present study, a small animal model for monitoring the changes of gastric pHi or intramucosal [H+] following challenge with the endotoxi...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2001.03432.x
更新日期:2001-03-01 00:00:00
abstract::1. Animal and human studies indicate that female sex hormones are protective against the development of coronary atherosclerosis. 2. Experiments on vascular smooth muscle cells suggest a direct effect of oestrogen on vascular tissue. Although oestrogen receptors (ER) in vascular tissues and an association between ER s...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.1996.tb02775.x
更新日期:1996-06-01 00:00:00
abstract::Drug-induced phospholipidosis (DIPL) is characterized by phospholipid storage in the lysosomes of affected tissues. Many severe effects and toxicities have been linked to DIPL. The aim of this study was to determine whether the endogenous opioid system is involved in chloroquine-induced phospholipidosis. The effect of...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.13332
更新日期:2020-09-01 00:00:00
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journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.13173
更新日期:2020-01-01 00:00:00
abstract::1. Oxidative stress (OS) is a biological entity indicated as being responsible for several pathologies, including diabetes. Diabetes can also be associated with human cirrhosis. Portal hypertension (PH), a major syndrome in cirrhosis, produces hyperdynamic splanchnic circulation and hyperaemia. The present study was d...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2004.03963.x
更新日期:2004-03-01 00:00:00
abstract::1. Strips of rabbit anococcygeus muscle were submaximally contracted by the addition of phenylephrine to the bath fluid. 2. Acetylcholine, dimethylphenylpiperazinium and electrical field stimulation caused relaxation. Relaxation induced by acetylcholine and field stimulation was blocked by tetrodotoxin but only the ac...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1976.tb00598.x
更新日期:1976-03-01 00:00:00
abstract::Hyperhomocysteine has become a critical risk for atherosclerosis and can stimulate proliferation and migration of vascular smooth muscle cells (VSMCs). N-methyl-D-aspartic acid receptor (NMDAR) is a receptor of homocysteine and mediates the effects of homocysteine on VSMCs. Bioinformatics analysis has shown NMDAR is a...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.12611
更新日期:2016-10-01 00:00:00
abstract::1. Plasma concentrations of prorenin were determined in a transgenic animal model of nephropathy induced by overexpression of transforming growth factor (TGF)-beta1 in the juxtaglomerular apparatus. 2. In both female and male mice, plasma concentrations of prorenin were higher in transgenic than in non-transgenic anim...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2000.03330.x
更新日期:2000-09-01 00:00:00
abstract::1. Intermittent bursts of activity are a robust feature of the discharges of sympathetic nerves. There are at least two major mechanisms producing such discharges: (i) phasic inputs influencing sympathetic circuits; and (ii) oscillators embedded within sympathetic networks. The functional significance of patterned and...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1046/j.1440-1681.2001.03414.x
更新日期:2001-01-01 00:00:00
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journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2002.03635.x
更新日期:2002-03-01 00:00:00
abstract::1. The present brief review examines some of the new developments in the area of circadian rhythm research. 2. The discovery of the mouse clock and m-per genes and their similarity to other clock genes like per and tim has provided new insight into the control of rhythms in vertebrates. In mice, these genes are expres...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.1998.tb02168.x
更新日期:1998-10-01 00:00:00
abstract::1. We tested the hypothesis that increasing myocardial cyclic GMP levels would reduce myocardial O2 consumption and areas of low O2 supply/consumption balance, using zaprinast, a selective cyclic GMP-phosphodiesterase inhibitor. 2. The study was conducted in three groups (vehicle, 10(-3) and 3 x 10(-3) mol/L zaprinast...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1994.tb02561.x
更新日期:1994-08-01 00:00:00
abstract::Azithromycin (AZM) has been used for the treatment of asthma and chronic obstructive pulmonary disease (COPD); however, the effects and underlying mechanisms of AZM remain largely unknown. The effects of AZM on airway smooth muscles (ASMs) and the underlying mechanisms were studied using isometric muscle force measure...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.13062
更新日期:2019-04-01 00:00:00
abstract::Urapidil had blocking activity on alpha 1-adrenoceptors in the rat isolated caudal artery (pA2 congruent to 7) and in the anaesthetized rat. Urapidil had no clonidine like agonistic activity on alpha 2-adrenoceptors in preparations of the guinea-pig ileum (prejunctional) or dog saphenous vein (post-junctional). Urapid...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1984.tb00289.x
更新日期:1984-07-01 00:00:00