Disease relevance of PGHS-2

• Pharmacologic modulation of iNOS and COX-2 activity may represent a therapeutic target for pigs with pleuropneumonia [1].
• OBJECTIVE: To determine the amount of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) activity in alveolar macrophages in response to Actinobacillus pleuropneumoniae (APP) by determining nitric oxide (NO) and prostaglandin E2 (PGE2) concentrations [1].
• BACKGROUND: Ischemia increases levels of prostaglandin H synthase-2 (PGHS-2) in neonatal brain and cerebral vasculature, but effects on the developing visual system are unknown [2].
• Relationship between NOC/oFQ, dynorphin, and COX-2 activation in impaired NMDA cerebrovasodilation after brain injury [3].
• We examined whether the selective COX-2 inhibitor NS398 would protect neuronal function after global hypoxia/ischemia (H/I) in piglets [4].

High impact information on PGHS-2

• Injured tissues treated with the selective COX-1 inhibitor SC-560 (5x10(-6) M) or the COX-2 inhibitor NS-398 (5x10(-6) M) recovered to control levels of resistance within three hours, associated with significant elevations of PGE and 6-keto-PGF1alpha compared with untreated tissues [5].
• Recovery of ischaemic injured porcine ileum: evidence for a contributory role of COX-1 and COX-2 [5].
• CONCLUSIONS: The results suggest that recovery of resistance is triggered by PGE and PGI2, which may be elaborated by either COX-1 or COX-2 [5].
• Both PGHS-1 and PGHS-2 contributed equivalently to light-induced prostaglandin synthesis, as shown after selective PGHS-2 blockers, but mRNA expression of PGHS-1 and 2 was not affected by light [6].
• Endometrial PTGS1 mRNA expression increased 2- to 3-fold after Day 10 of the estrous cycle and pregnancy, whereas PTGS2 mRNA expression increased 76-fold between Days 5 and 15 of the estrous cycle and pregnancy [7].

Chemical compound and disease context of PGHS-2

• Indomethacin pretreatment inhibited increases in mRNA and protein for PGHS-2 after ischemia, while 7-NI had little effect on increases in PGHS-2 immunoreactivity [8].
• COX-2-dependent contracting factors, such as thromboxane, contribute to aberrant pulmonary arterial responses in piglets exposed to 3 days of hypoxia [9].
• Cyclooxygenase-2 (COX-2) protein was detected immunohistochemically in formalin-fixed, paraffin wax-embedded lung tissues from 15 pigs with naturally occurring pleuropneumonia caused by Actinobacillus pleuropneumoniae [10].
• Cyclooxygenase-2 (COX-2) was detected and localized in 15 pigs with naturally occurring pleuropneumonia using a 437-base pair digoxigenin-labeled cDNA probe in an in situ hybridization protocol [11].
• Therefore, we studied the influence of the non-selective cyclooxygenase (COX) inhibitor diclofenac, a NSAID drug customarily used in the treatment of renal colic, and of NS-398, a selective COX-2 inhibitor, on induced contractions of the pig ureter [12].

Biological context of PGHS-2

• The JNK inhibitor SP-600125 (0.1 mM) significantly increased TER and resulted in COX-2 upregulation [13].
• The present study demonstrates that an increase in uterine epithelial PTGS2 expression occurs after Day 10 of the estrous cycle and early pregnancy in the pig [7].
• Administration of estrogen on Days 9 and 10 of gestation increased endometrial PTGS2 mRNA and protein on Day 10, but decreased PTGS2 mRNA and protein in lumenal epithelium (LE) on Day 12 of gestation compared to vehicle-treated gilts [7].
• Differences in gene frequencies between IOL vs C and COL vs C were 0.33 +/- 0.25 and 0.16 +/- 0.26 for PRLR, 0.35 +/- 0.20 and 0.15 +/- 0.24 for FSHbeta, and 0.16 +/- 0.16 and 0.08 +/- 0.18 for PTGS2 [14].
• Expression of eNOS, iNOS, and inducible (COX-2) and constitutive (COX-1) cyclooxygenase was examined with Western blotting and reverse transcription polymerase chain reaction [15].

Anatomical context of PGHS-2

• Because COX-2 expression is regulated in part by MAPKs, we postulated that MAPK pathways would play an integral role in recovery of injured mucosa [13].
• Mitogen-activated protein kinases regulate COX-2 and mucosal recovery in ischemic-injured porcine ileum [13].
• Immunostaining for nNOS displayed a different pattern from PGHS-2 in the hippocampus, and was mainly localized to the granule cell layer of the dentate gyrus and the mossy fiber layer [16].
• And third, the distribution of nNOS is different from PGHS-2 immunoreactivity in the cerebral cortex, hippocampus, and cerebellum [16].
• In addition, glial cells associated with microvessels in white matter showed PGHS-2 immunoreactivity [16].

Associations of PGHS-2 with chemical compounds

• Application of 5 x 10(6) PMNs to the serosal surface of ischemia-injured mucosa significantly enhanced recovery of TER (P < 0.05), an effect that was inhibited by the selective COX-2 inhibitor NS-398 (5 microM) and by an IL-1beta receptor antagonist (0.1 mg/ml) [17].
• Western blot analysis revealed that SB-203580 inhibited upregulation of COX-2 that was observed in untreated ischemic-injured mucosa, whereas PD-98059 had no effect on COX-2 expression [13].
• (2) Lipopolysaccharide could up-regulate the expression of some inflammatory mediators in PIMs, including TNF-alpha, IL-1beta, IL-6, IL-8, and COX-2, and these up-regulated expression of inflammatory mediators correlated with NF-kappaB activation [18].
• Our results suggest that NF-kappaB activation in PIMs followed by phagocytizing lipopolysaccharide resulted in the up-regulation of TNF-alpha, IL-1beta, IL-6, IL-8, and COX-2, which could be alleviated by dexamethasone [18].
• Inhibition of iNOS and COX-2 decreased NO and PGE2 production, respectively [1].

Other interactions of PGHS-2

• After treatment with IL-1beta, COX-2 immunoreactivity was detected in the wall of the gut in both neurons and nonneuronal cells [19].
• Based on chi-square analysis for homogeneity of genotypic frequencies, distributions for PRLR, FSHbeta, and PTGS2 were different among lines (P < 0.005) [14].
• Abundances of both COX-1 and prostacyclin synthase were reduced, whereas abundances of both COX-2 and thromboxane synthase were unaltered in pulmonary arteries from hypoxic piglets [20].

Analytical, diagnostic and therapeutic context of PGHS-2

• Real-time PCR revealed that increased mRNA COX-2 expression preceded increased COX-2 protein expression in response to IL-1beta [17].
• In cell culture, cloprostenol or phorbol 12, 13-didecanoate (PDD) (protein kinase C activator), induced PGHS-2 mRNA in luteal cells from both groups [21].
• After 2-12 h of reperfusion, samples of retina and visual cortex were collected for determinations of levels of PGHS-2 mRNA (RNase protection assay) or protein (immunohistochemistry and western blotting) [2].
• We examined the influence of COX inhibition on myocardial function after low-flow ischaemia and reperfusion, employing either ASA (100 micromol/l), the partially selective COX-2 inhibitor meloxicam (0.3 micromol/l and 3.0 micromol/l), or the highly selective COX-2 inhibitor SC 58125 (1.0 micromol/l and 3.0 microgmol/l) [22].
• In contrast, immunofluorescence for COX-2 was greatly increased in cerebral arteries and arterioles from animals exposed to asphyxia or ischemia [23].

References