High output of prostaglandins (PGs) are the hallmark of inflammatory and immune reactions. A rate-limiting step in the production of PGs is the presence of the enzyme cyclooxygenase (COX). COX exists as two isoforms: COX-1 which is constitutively expressed in most cells and COX-2 which is inducible by LPS, proinflammatory cytokines and other stimuli in cells involved in inflammation. The objective of this study was to determine the effect of nonsteroidal antiinflammatory drugs and proinflammatory cytokines on COX-2 expression in human macrophages. COX-2 specific (NS-398) and non-specific (aspirin, indomethacin and naproxen) inhibitors showed no effect on COX mRNA and protein expression induced by LPS. In contrast, the drugs markedly inhibited COX activity as measured by the accumulation of PGE2. The induction of COX-2 mRNA expression by LPS was rapid and sustained. However, LPS only transiently stimulated the transcription of COX-2 gene and activation of the transcription factor NF-kappaB. LPS stimulated the release of IL-1beta and TNF-alpha but these cytokines had no autocrine effect on the transcriptional or post-transcriptional regulation of COX-2. The presence of LPS was essential for the maintenance of high levels of long-lived COX-2 mRNA. As IFN-gamma is a major macrophage activating factor, we determined the role of this cytokine on COX-2 expression induced by exogenous IL-1beta. IFN-gamma-primed macrophages showed significantly lower levels of COX-2 mRNA, protein and PGE2 production compared to non-primed cells. IFN-gamma specifically decreased the transcriptional activation of COX-2 gene by IL-1beta but not by LPS without affecting the rate of mRNA decay. These results demonstrate that sustained production of PGE2 by macrophages in an inflammatory milieu can occur through the stabilization of COX-2 mRNA and revealed a role for IFN-gamma as an anti-inflammatory cytokine counteracting the expression of COX-2. A better understanding of COX-2 regulation will

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly worldwide. Due to the inadequacy of current pharmacotherapies, novel molecular targets must be sought as potential therapeutic candidates. Furthermore, there is a need for more efficient and cost-effective animal models of this pathology in order to accelerate in vivo investigations. / Our laboratory is in possession of human choroidal neovascular membranes which we examined for expression of cyclooxygenase (COX)-2. This expression was characterized in retinal pigment epithelial, vascular endothelial, and fibroblast cells and correlated with patient age. We also looked at the feasibility of creating a rabbit laser-injury model to adequately mimic human neovascular AMD. / Our results suggest that anti-COX-2 therapies may be beneficial to some patients with neovascular AMD. Moreover, there is strong potential for the development of clinically relevant choroidal neovascularization in rabbits using the laser-injury technique. This approach may yield a novel, cost-effective AMD model.

We have previously shown that non-specific blockade of the cyclooxygenase (COX) enzymes in skeletal muscle eliminates the normal increase in muscle protein synthesis following resistance exercise. The current study tested the hypothesis that this COX-mediated increase in postexercise muscle protein synthesis is specifically regulated by the COX-2 isoform. Sixteen males (23 ± 1 yr, 177 ± 2 cm, 81.5 ± 3.4 kg) were randomly assigned to one of two groups that received three doses of either a specific COX-2 inhibitor (celecoxib; 200 mg per dose, 600 mg total) or a placebo during the 24 hours following a single bout of resistance exercise with the knee extensors. Skeletal muscle fractional synthesis rate (FSR) was measured at rest and 24 hours postexercise using a primed constant infusion of [2H5]phenylalanine coupled with muscle biopsies of the vastus lateralis. Mixed muscle FSR was increased following exercise to a greater extent (206%, P<0.05) in the COX-2 group (0.052 ± 0.014 %Ih) as compared with the placebo group (0.017 ± 0.007 %Ih). These results suggest that the specific inhibition of the COX-2 isoform in human skeletal muscle causes a compensatory response in muscle protein synthesis. These data also highlight the involvement of the cyclooxygenase pathways in the regulation of muscle protein synthesis following resistance exercise. / School of Physical Education, Sport, and Exercise Science

Wernicke's encephalopathy is a neuropsychiatric disorder resulting from thiamine deficiency (TD) and is characterized by neuronal loss, astrocytic proliferation and microglial activation. Cyclooxygenases (COX) are enzymes which catalyze the first step in the synthesis of prostanoids. COX-1 is expressed constitutively and COX-2 is the inducible isoform. Groups of TD rats and pair-fed controls were killed at presymptomatic and symptomatic stages of encephalopathy. Cresyl violet and NeuN staining showed decreased numbers of neuronal cells in vulnerable regions (medial thalamus and inferior colliculus) but not in a spared region (frontal cortex). Numbers of GFAP-positive and OX-42-positive cells were increased at symptomatic stage of encephalopathy. Expression of COX-2 mRNA and neuronal COX-2 immunoreactivity were selectively increased in vulnerable regions of TD rats at symptomatic stages of encephalopathy. Nimesulide, a highly selective COX-2 inhibitor, lowered PGE2 levels and precipitated the progression of encephalopathy suggesting that COX-2 in this model is conferring neuroprotection.

No description available.

Diss. (sammanfattning) Göteborg : Univ. , 2007. / Härtill 4 uppsatser.

Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine and Royal Adelaide Hospital, Rheumatology Unit, 2004. / Includes list of publications arising from this thesis. Erratum attached to inside back cover. "25/03/2004." Includes bibliographical references (leaves 185-257).

Thesis (M.Sc.). / Written for the Dept. of Epidemiology, Biostatistics and Occupational Health. Title from title page of PDF (viewed 2008/07/30). Includes bibliographical references.

Thesis (Ph. D.)--University of Missouri-Columbia, 2007. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. "May 2007" Includes bibliographical references.

Thesis (M.S.)--University of Missouri-Columbia, 2008. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Includes bibliographical references.