Prostaglandin synthase 1 gene disruption in mice reduces arachidonic acid-induced inflammation and indomethacin-induced gastric ulceration

Langenbach, Robert; Morham, Scott G.; Tiano, Howard F.; Loftin, Charles D.; Ghanayem, Burhan I.; Chulada, Patricia C.; Mahler, Joel F.; Lee, Christopher A.; Goulding, Eugenia H.; Kluckman, Kimberly D.; Kim, H.S.; Smithies, Oliver

doi:10.1016/0092-8674(95)90126-4

Cited by 1,064 publications

(656 citation statements)

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“…Although LT appear to be the major mediators of AA-induced acute inflammation, it has been demonstrated that prostanoids produced via the COX pathways also play a role in this model (23,(32)(33)(34)(35)(36). Treatment of wild-type mice with the COX inhibitor INDO allowed us to examine the contribution of prostanoids to AA-induced cutaneous inflammation.…”

Section: Discussionmentioning

confidence: 99%

Genetic Factors Determine the Contribution of Leukotrienes to Acute Inflammatory Responses

Goulet

Byrum

Key

et al. 2000

The Journal of Immunology

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Leukotrienes (LT) are potent lipid mediators synthesized by the 5-lipoxygenase pathway of arachidonic acid (AA) metabolism. LT have been implicated in a broad spectrum of inflammatory processes. To investigate the influence of genetic factors on the contribution of LT to acute inflammation, we generated congenic 5-lipoxygenase-deficient 129, C57BL/6 (B6), and DBA/1Lac (DBA) mouse lines. Topical application of AA evoked a vigorous inflammatory response in 129 and DBA mice, whereas only a modest response was seen in B6 animals. The response to AA in 129 and DBA strains is LT dependent. In contrast, LT make little contribution to this response in B6 mice. AA-induced inflammation in B6 mice is prostanoid dependent, since this response was substantially reduced by treating B6 mice with a cyclooxygenase inhibitor. These data suggest that prostanoids are essential for AA-induced cutaneous inflammation in B6 mice, whereas LT are the major mediators of this response in 129 and DBA strains. In contrast, the response to AA in the peritoneal cavity is robust in the 129 and B6 strains, but was significantly blunted in DBA mice, showing that strain differences in the response to AA are tissue specific. Variations in these and other experimental models of inflammation appear to correlate directly with the ability of a particular mouse strain and a specific tissue to respond to LT, specifically LTC4. Taken together, these findings indicate that the relative contribution of prostanoids and LT to inflammatory responses is variable not only between strains but also between different tissues within these inbred mouse lines.

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Section: Discussionmentioning

confidence: 99%

Genetic Factors Determine the Contribution of Leukotrienes to Acute Inflammatory Responses

Goulet

Byrum

Key

et al. 2000

The Journal of Immunology

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“…Male COX-1 -/-, COX-1 +/+ , COX-2 -/-, COX-2 +/-, and COX-2 +/+ mice maintained on a C57Bl/6-129/Ola background for over 35 generations [35,41] were received at our animal facility at 6 weeks of age from a private NIEHS colony maintained by Taconic Farms (Germantown, NY) separately from their commercially available colony. In order to prevent the inclusion of strain or genetic background confounders between COX deficient and wild type mice, all of the mice used in this study were derived from a maintenance colony of COX-1 +/-or COX-2 +/-males and females, as previously described [35,41,64]. Specifically, all mice used in this study were progeny derived from heterozygous by heterozygous matings and therefore all contained the same strain and genetic background.…”

Section: Animal Housingmentioning

confidence: 99%

Altered GABAergic neurotransmission is associated with increased kainate-induced seizure in prostaglandin-endoperoxide synthase-2 deficient mice

Toscano

Ueda

Tomita

et al. 2008

Brain Research Bulletin

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Excitotoxicity involves over activation of brain excitatory glutamate receptors and has been implicated in neurological, neurodegenerative and neuropsychiatric diseases. Metabolism of arachidonic acid (AA) through the phospholipase A 2 (PLA 2 )/ prostaglandin-endoperoxide synthase (PTGS) pathway is increased after excitotoxic stimulation. However, the individual roles of the PTGS isoforms in this process are not well established. We assessed the role of the PTGS isoforms in the process of excitotoxicity by exposing mice deficient in either PTGS-1 (PTGS-1 -/-) or PTGS-2 (PTGS-2 -/-) to the rototypic excitotoxin, kainic acid (KA). Seizure intensity and neuronal damage were significantly elevated in KA-exposed PTGS-2 -/-, but not in PTGS-1 -/-, mice. The increased susceptibility was not associated with an alteration in KA receptor binding activity or mediated through the CB1 endocannabinoid receptor. The frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) was decreased in the CA1 pyramidal neurons of PTGS-2 -/-mice, suggesting an alteration of GABAergic function. In wild-type mice, six weeks treatment with the PTGS-2 selective inhibitor celecoxib recapitulated the increased susceptibility to KA-induced excitotoxicity observed in PTGS-2 -/-mice, further supporting the role of PTGS-2 in the excitotoxic process. The increased susceptibility to KA was also associated with decreased brain levels of PGE 2 , a biomarker of PTGS-2 activity. Our results suggest that PTGS-2 activity and its specific products may modulate neuronal excitability by affecting GABAergic neurotransmission. Further, inhibition of PTGS-2 but not PTGS-1, may increase the susceptibility to seizures.

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“…However, studies have indicated that this image is more complex, and both constitutively expressed Cox2 and inducible Cox1 genes have been described somewhat depending on tissue (Breder et al 1995;Harris et al 2001). They also seem to be differentially regulated, and have shown to have different function in knock-out mice, whereas COX1 seems to have housekeeping function while COX-2, accounts for the elevated production of prostaglandins (Dinchuk et al 1995;Langenbach et al 1995;Morham et al 1995). In teleosts there are additional copies of cox2, probably due to genome duplication.…”

Section: Introductionmentioning

confidence: 99%

Stress and expression of cyclooxygenases (cox1, cox2a, cox2b) and intestinal eicosanoids, in Atlantic salmon, Salmo salar L.

Olsen

Svardal

Eide

et al. 2011

Fish Physiol Biochem

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Havforskningsinstituttets institusjonelle arkiv Brage IMR - Institutional repository of the Institute of Marine Research b r a g e i m rDette er forfatters siste versjon av den fagfellevurderte artikkelen, vanligvis omtalt som postprint. I Brage IMR er denne artikkelen ikke publisert med forlagets layout fordi forlaget ikke tillater dette. Du finner lenke til forlagets versjon i Brage-posten. Det anbefales at referanser til artikkelen hentes fra forlagets side. Ved lenking til artikkelen skal det lenkes til post i Brage IMR, ikke direkte til pdf-fil.This is the author's last version of the article after peer review and is not the publisher's version, usually referred to as postprint. You will find a link to the publisher's version in Brage IMR. It is recommended that you obtain the references from the publisher's site.Linking to the article should be to the Brage-record, not directly to the pdf-file. Foto: Leif NøttestadFish Physiology and Biochemistry Stress and expression of cyclooxygenases (cox1, cox2a, cox2b) and intestinal eicosanoids, in Atlantic salmon, Salmo salar.--Manuscript Draft-- Abstract: Prostaglandin H synthetases (cyclooxygensases) catalyze the initial reactions leading to prostanoids in animals. They form interesting links between diet and fish physiology as the type and nature of eicosanoids are affected by dietary lipid sources. Their expression is likely to be affected by tissues and also altered environmental conditions leading to altered amount and ratio of eicosanoids. These mechanisms are however poorly understood in fish. In the present study, Atlantic salmon Salmo salar (1000g, 10°C, seawater) were subjected to acute chasing stress. Liver, kidney, spleen, gill, muscle, midgut and hindgut were extracted before and 1h post stress and analyzed for mRNA expression of cox1, cox2a and cox2b. Intestinal samples were furthermore sampled over 24h for both cox expression and eicosanoid content. Results show a highly variable but consecutively expression of cox1, cox2a, cox2b in most tissues analyzed. Low levels were only found for cox2a in liver and cox2b in liver and kidney. The study reveals the general trend that cox1 is about 10 times the level of cox2b which again is about 10 times the level of cox2a. Cox2b shows the highest level of expression in the gills indicating a possible higher requirement for this protein in gills. Imposing stress to the fish induce a temporal increase in the expression of cox2a in the midgut while the gene expression of the other genes is not affected in any of the tissues analyzed. There is however a general tendency to increased expression of both cox2 genes that merits further studies. Stress had a profound effect on the intestinal eicosanoid content which showed a general decrease in midgut sections after stress that persisted for at least 24h. Response to Reviewers:We have checked the manuscript for spelling erros. For the notations of genes and proteins as suggested by the referee, we have doen the following, which is the current convention on labelling. We ...

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Prostaglandin synthase 1 gene disruption in mice reduces arachidonic acid-induced inflammation and indomethacin-induced gastric ulceration

Cited by 1,064 publications

References 58 publications

Genetic Factors Determine the Contribution of Leukotrienes to Acute Inflammatory Responses

Genetic Factors Determine the Contribution of Leukotrienes to Acute Inflammatory Responses

Altered GABAergic neurotransmission is associated with increased kainate-induced seizure in prostaglandin-endoperoxide synthase-2 deficient mice

Stress and expression of cyclooxygenases (cox1, cox2a, cox2b) and intestinal eicosanoids, in Atlantic salmon, Salmo salar L.

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