Abstract:
:Cyclooxygenase (COX) has two isoforms. Generally, COX 1 is constitutively expressed in most tissues, where it maintains physiological processes; inducible COX 2 is considered a pro-inflammatory enzyme and a chief target for the treatment of inflammatory diseases. Here we present evidence that COX 2 may have anti-inflammatory properties. In carrageenin-induced pleurisy in rats, the predominant cells at 2 hours are polymorphonuclear leucocytes, whereas mononuclear cells dominate from 24 hours until resolution at 48 hours. In this model, COX 2 protein expression peaked initially at 2 hours, associated with maximal prostaglandin E2 synthesis. However, at 48 hours there was a second increase in COX 2 expression, 350% greater than that at 2 hours. Paradoxically, this coincided with inflammatory resolution and was associated with minimal prostaglandin E2 synthesis. In contrast, levels of prostaglandin D2, and 15deoxy delta(12-14)prostaglandin J2 were high at 2 hours, decreased as inflammation increased, but were increased again at 48 hours. The selective COX 2 inhibitor NS-398 and the dual COX 1/COX 2 inhibitor indomethacin inhibited inflammation at 2 hours but significantly exacerbated inflammation at 48 hours. This exacerbation was associated with reduced exudate prostaglandin D2 and 15deoxy delta(12-14)prostaglandin J2 concentrations, and was reversed by replacement of these prostaglandins. Thus, COX 2 may be pro-inflammatory during the early phase of a carrageenin-induced pleurisy, dominated by polymorphonuclear leucocytes, but may aid resolution at the later, mononuclear cell-dominated phase by generating an alternative set of anti-inflammatory prostaglandins.
journal_name
Nat Medjournal_title
Nature medicineauthors
Gilroy DW,Colville-Nash PR,Willis D,Chivers J,Paul-Clark MJ,Willoughby DAdoi
10.1038/9550keywords:
subject
Has Abstractpub_date
1999-06-01 00:00:00pages
698-701issue
6eissn
1078-8956issn
1546-170Xjournal_volume
5pub_type
杂志文章相关文献
NATURE MEDICINE文献大全abstract::The use of genetically manipulated mouse models, gene and protein discovery and the cataloguing of genetic mutations have each allowed us to obtain new insights into skeletal morphogenesis and remodeling. These techniques have made it possible to identify molecules that are obligatory for specific cellular functions, ...
journal_title:Nature medicine
pub_type: 杂志文章,评审
doi:10.1038/nm1593
更新日期:2007-07-01 00:00:00
abstract::Hereditary hemochromatosis and transfusional iron overload are frequent clinical conditions associated with progressive iron accumulation in parenchymal tissues, leading to eventual organ failure. We have discovered a new mechanism to reverse iron overload-pharmacological modulation of the divalent metal transporter-1...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1542
更新日期:2007-04-01 00:00:00
abstract::Given the variation in the HIV-1 viral load (VL) set point across subjects, as opposed to a fairly stable VL over time within an infected individual, it is important to identify the characteristics of the host and virus that affect VL set point. Although recently infected individuals with multiple phylogenetically lin...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3932
更新日期:2015-10-01 00:00:00
abstract::Cytochrome P450 3A4 is an important mediator of drug catabolism that can be regulated by the steroid and xenobiotic receptor (SXR). We show here that SXR also regulates drug efflux by activating expression of the gene MDR1, which encodes the protein P-glycoprotein (ABCB1). Paclitaxel (Taxol), a commonly used chemother...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/87912
更新日期:2001-05-01 00:00:00
abstract::The notoriously drug-resistant bug MRSA has made headlines for years, but a whole other class of bacteria may prove even more troublesome. These microbes, Gram-negative bacteria, are increasingly a threat--and yet not a single late-stage drug in development specifically targets them. Christian Torres follows one man's...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0610-628
更新日期:2010-06-01 00:00:00
abstract::Sexual transmission is the most frequent (86%) route of adult HIV-1 transmission worldwide. In the absence of a prophylactic anti-HIV vaccine, other methods of preventing infection should be implemented. Virucidal spermicides have been considered for this purpose, but their application is contraindicated by adverse ef...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0296-230
更新日期:1996-02-01 00:00:00
abstract::The severe disease atypical measles occurred when individuals immunized with a poorly protective inactivated vaccine contracted measles, and was postulated to be due to a lack of fusion-inhibiting antibodies. Here, rhesus macaques immunized with formalin-inactivated measles vaccine developed transient neutralizing and...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/9473
更新日期:1999-06-01 00:00:00
abstract::Activating mutations in genes encoding G protein α (Gα) subunits occur in 4-5% of all human cancers, but oncogenic alterations in Gβ subunits have not been defined. Here we demonstrate that recurrent mutations in the Gβ proteins GNB1 and GNB2 confer cytokine-independent growth and activate canonical G protein signalin...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3751
更新日期:2015-01-01 00:00:00
abstract::Treating KRAS-mutant lung adenocarcinoma (LUAD) remains a major challenge in cancer treatment given the difficulties associated with directly inhibiting the KRAS oncoprotein. One approach to addressing this challenge is to define mutations that frequently co-occur with those in KRAS, which themselves may lead to thera...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.4407
更新日期:2017-11-01 00:00:00
abstract::Diabetes in non-obese diabetic (NOD) mice is mediated by pathogenic T-helper type 1 (Th1) cells that arise because of a deficiency in regulatory or suppressor T cells. V alpha 14-J alpha 15 natural killer T (NKT) cells recognize lipid antigens presented by the major histocompatibility complex class I-like protein CD1d...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0901-1052
更新日期:2001-09-01 00:00:00
abstract::Approximately 1-5% of breast cancers are attributed to inherited mutations in BRCA1 or BRCA2 and are selectively sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors. In other cancer types, germline and/or somatic mutations in BRCA1 and/or BRCA2 (BRCA1/BRCA2) also confer selective sensitivity to PARP inhibitors....
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.4292
更新日期:2017-04-01 00:00:00
abstract::Idiopathic voiding disorders affect up to 10-15% of men and women. We describe bladder abnormalities in mice with targeted deletion of the gene for neuronal nitric oxide synthase which model the clinical disorders. The mice possess hypertrophic dilated bladders and dysfunctional urinary outlets which do not relax in r...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0597-571
更新日期:1997-05-01 00:00:00
abstract::Epstein-Barr virus is ubiquitous and is causally implicated in lymphoid and epithelial malignancies. Virus invades oropharyngeal mucosa and establishes latency in B lymphocytes. Reactivating lymphocytes shed virus into saliva for spread to new hosts. A complex of three virus glycoproteins, gH, gL and gp42, is essentia...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0602-594
更新日期:2002-06-01 00:00:00
abstract::The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) is of global concern: the virus has caused severe respiratory illness, with 111 confirmed cases and 52 deaths at the time of this article's publication. Therapeutic interventions have not been evaluated in vivo; thus, patient management relies ex...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3362
更新日期:2013-10-01 00:00:00
abstract::Sepsis remains a global clinical problem. By using the mouse cecal ligation and puncture model of sepsis, here we identify an important aspect of mast cell (MC)-dependent, innate immune defenses against Gram-negative bacteria by demonstrating that MC protease activity is regulated by interleukin-15 (IL-15). Mouse MCs ...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1615
更新日期:2007-08-01 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Nature medicine
pub_type: 已发布勘误
doi:10.1038/s41591-020-1016-z
更新日期:2020-09-01 00:00:00
abstract::Pulmonary hypertension (PH) is characterized by increased proliferation and apoptosis resistance of pulmonary artery smooth muscle cells (PASMCs). Forkhead box O (FoxO) transcription factors are key regulators of cellular proliferation. Here we show that in pulmonary vessels and PASMCs of human and experimental PH lun...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3695
更新日期:2014-11-01 00:00:00
abstract::Movement towards or away from a given stimulus guides the directional migration of prokaryotes, simple eukaryotes and neurons. As bi-directional cues may influence entry and exit of immune effector cells from tissue sites, we evaluated the migratory responses of T-cell subsets to varying concentrations of the chemokin...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/75022
更新日期:2000-05-01 00:00:00
abstract::Deep brain stimulation (DBS) is a widely used neurosurgical approach to treating tremor and other movement disorders. In addition, the use of DBS in a number of psychiatric diseases, including obsessive-compulsive disorders and depression, is currently being tested. Despite the rapid increase in the number of individu...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1693
更新日期:2008-01-01 00:00:00
abstract::Insulin receptor substrate (IRS)-1 and IRS-2 have dominant roles in the action of insulin, but other substrates of the insulin receptor kinase, such as Gab1, c-Cbl, SH2-B and APS, are also of physiological relevance. Although the protein downstream of tyrosine kinases-1 (Dok1) is known to function as a multisite adapt...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1706
更新日期:2008-02-01 00:00:00
abstract::Ethylmalonic encephalopathy is caused by mutations in ETHE1, a mitochondrial matrix sulfur dioxygenase, leading to failure to detoxify sulfide, a product of intestinal anaerobes and, in trace amounts, tissues. Metronidazole, a bactericide, or N-acetylcysteine, a precursor of sulfide-buffering glutathione, substantiall...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.2188
更新日期:2010-08-01 00:00:00
abstract::Targeted gene transduction to specific tissues and organs through intravenous injection would be the ultimate preferred method of gene delivery. Here, we report successful targeting in a living animal through intravenous injection of a lentiviral vector pseudotyped with a modified chimeric Sindbis virus envelope (term...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1192
更新日期:2005-03-01 00:00:00
abstract::TRK fusions are found in a variety of cancer types, lead to oncogenic addiction, and strongly predict tumor-agnostic efficacy of TRK inhibition1-8. With the recent approval of the first selective TRK inhibitor, larotrectinib, for patients with any TRK-fusion-positive adult or pediatric solid tumor, to identify mechani...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/s41591-019-0542-z
更新日期:2019-09-01 00:00:00
abstract::Our understanding of Alzheimer's disease (AD) pathophysiology remains incomplete. Here we used quantitative mass spectrometry and coexpression network analysis to conduct the largest proteomic study thus far on AD. A protein network module linked to sugar metabolism emerged as one of the modules most significantly ass...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/s41591-020-0815-6
更新日期:2020-05-01 00:00:00
abstract::We previously demonstrated that low biosynthesis of ω-3 fatty acid-derived proresolution mediators, termed protectins, is associated with an impaired global resolution capacity, inflammation and insulin resistance in obese high-fat diet-fed mice. These findings prompted a more direct study of the therapeutic potential...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3549
更新日期:2014-06-01 00:00:00
abstract::Genetic variants of human and simian immunodeficiency virus (HIV and SIV) that evolve during the course of infection and progression to AIDS are phenotypically and antigenically distinct from their progenitor viruses present at early stages of infection. However, it has been unclear how these late variants, which are ...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/8414
更新日期:1999-05-01 00:00:00
abstract::CD4-unhelped CD8(+) T cells are functionally defective T cells primed in the absence of CD4(+) T cell help. Given the co-stimulatory role of natural-killer group 2, member D protein (NKG2D) on CD8(+) T cells, we investigated its ability to rescue these immunologically impotent cells. We demonstrate that augmented co-s...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.2683
更新日期:2012-02-26 00:00:00
abstract::In the nervous system, NMDA receptors (NMDARs) participate in neurotransmission and modulate the viability of neurons. In contrast, little is known about the role of NMDARs in pancreatic islets and the insulin-secreting beta cells whose functional impairment contributes to diabetes mellitus. Here we found that inhibit...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3822
更新日期:2015-04-01 00:00:00
abstract::An effective acquired immune response to infectious agents mediated by HLA-restricted T-cell recognition can target different stages of disease pathogenesis. We show here that three distinct HLA alleles known to alter the overall rate of AIDS progression act during distinct intervals after HIV-1 infection. The discret...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1333
更新日期:2005-12-01 00:00:00
abstract::The incidence of chronic pain is estimated to be 20-25% worldwide. Few patients with chronic pain obtain complete relief from the drugs that are currently available, and more than half report inadequate relief. Underlying the challenge of developing better drugs to manage chronic pain is incomplete understanding of th...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.2235
更新日期:2010-11-01 00:00:00