Cyclooxygenase-2: regulation and relevance in inflammation.
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Animals↗
Biomedical subjects
J A Mitchell
Publications and source records attributed to J A Mitchell.
Nitric oxide synthase activity is elevated in inflammatory lung disease in humans.
We have characterised nitric oxide (NO) synthase activity in lung samples from patients with inflammatory lung disease compared to that in normal donor lung. NO synthase activity was measured by the ability of tissue homogenates to convert L-arginine to L-citrulline. Higher levels of NO synthase activity were found in samples from patients with inflammatory lung disease (mild asthma, cystic fibrosis, obliterative bronchiolitis after lung transplantation) compared to samples from healthy donors. NO synthase activity in all samples was mainly dependent on the presence of extracellular Ca2+. The increased NO synthase activity in diseased-lung samples suggests a modulatory role for nitric oxide in lung inflammation.
Adolescent↗
Cloning and characterization of cbl-b: a SH3 binding protein with homology to the c-cbl proto-oncogene.
We have cloned a new gene, cbl-b, with homology to the c-cbl proto-oncogene. A large protein is predicted (approx. MW 108,000) that has a proline rich domain, a nuclear localization signal, a C3HC4 zinc finger and a putative leucine zipper. There is striking nucleotide and amino acid homology to the c-cbl proto-oncogene most notably in the structural motifs described above. Cbl-b is expressed in normal and malignant mammary epithelial cells, in a variety of normal tissues, and in hematopoietic tissue and cell lines. Cbl-b expressions is up-regulated with macrophage/monocyte differentiation of the HL60 and U937 cell lines. There is direct association of the cbl-b protein with the Src Homology 3 domains of several proteins including signaling, cytoskeletal and adaptor proteins. Our data suggest that cbl-b encodes a protein which can interact with signal transduction proteins to regulate their function or to be regulated by them. Together, cbl-b and c-cbl are members of a novel family of proto-oncogenes involved in signal transduction.
Animals↗
Comparison of the induction of cyclooxygenase and nitric oxide synthase by endotoxin in endothelial cells and macrophages.
Endotoxin causes the expression of inducible nitric oxide (NO) synthase and cyclooxygenase-2. We have compared the ability of endotoxin to increase the activities of these enzymes in bovine aortic endothelial cells and the macrophage cell line (J774.2). Endotoxin (1 microgram ml-1; for 24 h) caused a time-dependent increase in the accumulation of cyclooxygenase metabolites from endogenous arachidonic acid, in both cell types. Cyclooxygenase activity towards exogenous arachidonic acid (30 microM; for 15 min) was also increased in both cell types. Endothelial cells and macrophages also contained comparable amounts of cyclooxygenase-2 protein after incubation with endotoxin for 24 h which was prevented by pretreatment with cycloheximide (10 micrograms ml-1; 30 min prior to endotoxin). Endotoxin for 24 h caused a time-dependent increase in nitrite accumulation in macrophages, but not in endothelial cells. Thus, endotoxin increased cyclooxygenase activity and induced cyclooxygenase-2 protein in endothelial cells and macrophages. Endotoxin also increased NO synthase activity in macrophages, but not in endothelial cells.
Amino Acid Oxidoreductases↗
Distribution of cyclooxygenase isoforms in murine chronic granulomatous inflammation. Implications for future anti-inflammatory therapy.
Inhibition of the enzyme cyclooxygenase (COX) is the basis for the mechanism of action of non-steroidal anti-inflammatory drugs (NSAIDs). COX exists as a constitutive (COX-1) and a mitogen-inducible (COX-2) isoform. The relative contribution of COX-1 and COX-2 to inflammation is unknown. This study investigated COX activity and the distribution of COX-1 and COX-2 during the development of a murine air pouch model of chronic granulomatous inflammation. COX activity progressively rose and was maximal at day 14. Of the COX metabolites measured, PGE2 was the greatest > 6-keto PGF1a > TXB2 > PGF2a. By day 7, COX-2-labelled fibroblast- and macrophage-like cells were observed and their number and distribution increased with time. At all time points, endothelial cells of venules in the loose connective tissue of the dermis showed immunoreactivity for COX-2. After day 14, labelling of capillaries in the granuloma was also observed. This study is the first to show that COX-2 is the predominant COX isoform in all stages of the inflammatory response. These results suggest that selective inhibition of COX-2 may prove more beneficial, with fewer gastric and renal side-effects, than existing NSAID therapy for the treatment of chronic inflammatory diseases.
Animals↗
Analysing work performance problems--methods and their effectiveness.
This paper explores methods of analysing work performance problems. It begins by looking at what can be understood by the term 'work performance problems' and offers a definition. The author clarifies the differences between work performance problems and negative work behaviours, to eliminate any confusion that may exist. There follows a review of some possible causes of work performance problems, as identified by a number of writers. Eight methods for analysing work performance problems are described. The difficulties of evaluating the effectiveness of methods for analysing work performance problems are highlighted and the range of variables that need to be accounted for are discussed.
Employee Performance Appraisal↗
Methods of randomized controlled clinical trials in health services research.
The randomized controlled clinical trial is an increasingly used method in health services research. Analysis of methodology is needed to accelerate practical implementation of trial results, select trials for meta-analysis, and improve trial quality in health services research. The objectives of this study are to explore the methodology of health services research trials, create and validate a streamlined quality evaluation tool, and identify frequent quality defects and confounding effects on quality. The authors developed a quality questionnaire that contained 20 evaluation criteria for health services research trials. One hundred one trials from the Columbia Registry of Controlled Clinical Trials were evaluated using the new quality tool. The overall agreement between independent reviewers, Cohen's kappa, was 0.94 (+/- 0.01). Of a possible score of 100, the trials received an average score of 54.8 (+/- 12.5). Five evaluation criteria indicated significant quality deficiencies (sample size, description of case selection, data on possible adverse effects, analysis of secondary effect variables, and retrospective analysis). The quality of study characteristics was significantly weaker than the quality of reporting characteristics (P < 0.001). The total average scores of Medline-indexed journals were better than the non-Medline-indexed journals (P < 0.001). There was a positive correlation between the overall quality and year of publication (R = 0.21, P < 0.05). The authors conclude that the new quality evaluation tool leads to replicable results and there is an urgent need to improve several study characteristics of clinical trials. In comparison to drug trials, site selection, randomization, and blinding often require different approaches in health services research.
Evaluation Studies as Topic↗
Co-induction of nitric oxide synthase and cyclo-oxygenase: interactions between nitric oxide and prostanoids.
1. Lipopolysaccharide (LPS) co-induces nitric oxide synthase (iNOS) and cyclo-oxygenase (COX-2) in J774.2 macrophages. Here we have used LPS-activated J774.2 macrophages to investigate the effects of exogenous or endogenous nitric oxide (NO) on COX-2 in both intact and broken cell preparations. NOS activity was assessed by measuring the accumulation of nitrite using the Griess reaction. COX-2 activity was assessed by measuring the formation of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) by radioimmunoassay. Western blot analysis was used to determine the expression of COX-2 protein. We have also investigated whether endogenous NO regulates the activity and/or expression of COX in vivo by measuring NOS and COX activity in the lung and kidney, as well as release of prostanoids from the perfused lung of normal and LPS-treated rats. 2. Incubation of cultured murine macrophages (J774.2 cells) with LPS (1 microgram ml-1) for 24 h caused a time-dependent accumulation of nitrite and 6-keto-PGF1 alpha in the cell culture medium which was first significant after 6 h. The formation of both 6-keto-PGF1 alpha and nitrite elicited by LPS was inhibited by cycloheximide (1 microM) or dexamethasone (1 microM). Western blot analysis showed that J774.2 macrophages contained COX-2 protein after LPS administration, whereas untreated cells contained no COX-2. 3. The accumulation of 6-keto-PGF1 alpha in the medium of LPS-activated J774.2 macrophages was concentration-dependently inhibited by chronic (24 h) exposure to sodium nitroprusside (SNP; 1-1000 microM). Sodium nitroprusside (1-1000 microM) also acutely (30 min) inhibited COX-2 activity in broken cell preparations of LPS-activated (12 h) J774.2 macrophages, in a similar concentration dependent manner. Addition of adrenaline (5 mM) and glutathione (0.1 mM) increased the activity of COX-2 in broken cell preparations. In the presence of these co-factors, SNP inhibited prostanoid production only at the highest concentration used (1 mM). When J774.2 cells were incubated in the presence of LPS (1 microg ml-1) and NG-monomethyl-L-arginine (L-NMMA: 1 mM) for 12 h, SNP at the highest concentration used (1 mM) acutely (30 min) inhibited the activity of COX-2 in cell homogenates with co-factors. However, when J774.2 macrophages were incubated for 24 or 12 h with LPS (1 microg ml-1)and L-NMMA (1 mM), the addition of SNP (0.001-1I000 microM) increased in a concentration-dependent manner the accumulation of 6-keto-PGF1a in intact cells (measured at 24 h) and COX-2 activity in cell homogenates in the presence of co-factors (determined at 12 h). SNP (1 mM; together with LPS for 12 h)decreased the amount of COX-2 protein induced by LPS in J774.2 macrophages.4. Indomethacin (30 1AM) abolished the formation of 6-keto-PGFa by LPS-activated macrophages, but had no effect on the release of nitrite. Conversely, L-NMMA, at the highest concentrations used (1 and 10 mM), increased the release of 6-keto-PGFIa an effect which was reversed by excess L-arginine (3 mM)but not by D-arginine. Similarly, the decrease in nitrite formation caused by L-NMMA was partially reversed by L-arginine (3 mM), but not by D-arginine. L-NMMA (10 mM; together with LPS for 12 h)increased the amount of COX-2 protein induced by LPS in J774.2 macrophages.5. In separate experiments, J774.2 macrophages were activated with LPS (1 microg ml-1), and L-NMMA(10 mM) was added for various times (0.5-24 h) before the collection of mediun at 24 h. L-NMMAenhanced the release of 6-keto-PGFI,, in a time-dependent manner, with the maximal enhancement seen when the NOS inhibitor was incubated with the cells for 24 h. 6. In experiments on male Wistar rats, we investigated the effect of L-NMMA on the release of prostanoids (6-keto-PGF1a prostaglandin E2, thromboxane B2) elicited by arachidonic acid (AA,30nmol) from ex vivo perfused kidneys and lungs. The release from the organs from normal and LPS-treated rats was unaffected by L-NMMA intraperitoneally (30 mg kg-1) for 6 h together with LPS(5 mg kg-1) or LPS vehicle. Similarly, acute (5 min) in vitro exposure to L-NMMA (1 mM) of the perfused organs from control and LPS-treated animals did not change the release of prostanoids elicited by AA (30 nmol).7. These results show that LPS causes the induction of iNOS and COX-2 in J774.2 macrophages. The co-release of NO and PGI2 induced by LPS is dependent on protein synthesis and occurs after a lag-time of 6-12 h. The formation of COX metabolites has no effect on NOS activity whereas NO inhibits both COX-2 activity and induction. These results demonstrate that NOS and COX can be co-induced in vitro and that under these conditions large amounts of NO inhibit the degree of COX expression and activity.In the absence of endogenous NO, lesser amounts of exogenous NO increase the activity of COX-2. In those situations in vivo when the level of NO induction is relatively low, NO does not regulate the increased activity of COX.
Amino Acid Oxidoreductases↗
Nitric oxide synthase in the rat fallopian tube is regulated during the oestrous cycle.
Nitric oxide produced from L-arginine by nitric oxide synthase (NOS) acts in a variety of biological processes via the stimulation of guanylyl cyclase and subsequent elevation of cGMP. Constitutive, calcium-dependent isoforms of NOS are found in endothelial cells (eNOS) and neurones (nNOS), while macrophages express an inducible, calcium-independent isoform (iNOS) in response to the action of certain cytokines or bacterial endotoxin. While the regulation of NOS by exogenous glucocorticoids and steroid hormones is well documented, the effects of endogenous steroid hormones on NOS activity, such as those released during the oestrous cycle, is unknown. Here we demonstrate, using specific antibodies for eNOS, nNOS and iNOS, the presence of NOS in the epithelium of rat fallopian tubes at pro-oestrus, late pro-oestrus, oestrus, metoestrus and dioestrus. Western blot analysis of rat fallopian tube homogenates revealed a protein band at approximately 125 kDa which was recognised by antibodies to different isoforms of NOS, but no bands at the expected molecular weights (eNOS, 140 kDa; nNOS, 160 kDa; iNOS, 135 kDa). NOS activity in fallopian tubes was measured by the conversion of L-[3H]arginine to L-[3H]citrulline. Both calcium-dependent and -independent NOS activities were present. However, in late pro-oestrus when circulating oestrogens are low, NOS activity was reduced in comparison to all other stages of the oestrous cycle. Thus we show that NOS is present in the epithelial lining of the fallopian tube and is recognised at a previously undescribed molecular weight.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Negative work behaviours: their impact on disabled people seeking work.
This paper looks at work behaviours which prevent an individual from getting and keeping a job, and then reviews how these behaviours might be changed. The term 'work behaviours' is examined and a definition for the term is proposed. Possible causes of negative work behaviours are cited, along with the way they might manifest themselves. A diagram demonstrating visually the causes and manifestations of negative work behaviours is shown. The potential for changing work behaviors is discussed, followed by a review of possible techniques that can affect such a change. Direct and indirect techniques of behaviour change are described. Direct behaviour change is seen to be preferable to indirect change, and the author looks briefly at nine methods of direct behaviour change.
Attitude↗
Inducible isoforms of cyclooxygenase and nitric-oxide synthase in inflammation.
Cyclooxygenase (COX) converts arachidonic acid to prostaglandin H2, which is further metabolized to prostanoids. Two isoforms of COX exist: a constitutive (COX-1) and an inducible (COX-2) enzyme. Nitric oxide is derived from L-arginine by isoforms of nitric-oxide synthase (NOS; EC 1.14.13.39): constitutive (cNOS; calcium-dependent) and inducible (iNOS; calcium-independent). Here we have investigated inducible isoforms of COX and NOS in the acute, chronic, and resolving stages of a murine air pouch model of granulomatous inflammation. COX and NOS activities were measured in skin samples in the acute phase, up to 24 h. Activities in granulomatous tissue were measured at 3, 5, 7, 14, and 21 days for the chronic and resolving stages of inflammation. COX-1 and COX-2 proteins were assessed by Western blot. COX activity in the skin increased over the first 24 h and continued to rise up to day 14. COX-2 protein rose progressively, also peaking at day 14. COX-1 protein remained unaltered throughout. The iNOS activity increased over the first 24 h in the skin, with a further major increase in the granulomatous tissue between days 3 and 7, followed by a decrease at day 14 and a further increase at day 21. The rise in COX and NOS activities in the skin during the acute phase reinforces the proinflammatory role for prostanoids and suggests one also for nitric oxide. However, in the chronic and resolving stages, a dissociation of COX and NOS activity occurred. Thus, there may be differential regulation of these enzymes, perhaps due to the changing pattern of cytokines during the inflammatory response.
Amino Acid Oxidoreductases↗
Immunocytochemical detection of oxytocin in the supraependymal neuronal complex of the golden hamster.
A system of intraventricular neuronal perikarya and processes known as the supraependymal neuronal complex (SENC) is located on the floor of the third ventricle and innervates the neurohypophysis of the golden hamster (Mesocricetus auratus). Immunocytochemical techniques were used to determine if oxytocin and/or vasopressin are present in the neuronal elements of the SENC. Oxytocinergic fibers were observed to breach the ependyma of the median eminence and enter the neuropil of the SENC. Some of these fibers traverse the SENC to reach the adjacent ependymal surface and terminate on the floor of the third ventricle while others terminate within the neuropil of the SENC. These oxytocinergic fibers may be involved in the secretion of oxytocin into the cerebrospinal fluid (CSF). Vasopressinergic fibers were detected in the neuropil of the SENC in only one of four specimens examined and are assumed to be aberrant processes from the hypothalamo-neurohypophysial tract. Neither oxytocin nor vasopressin were detected in the neurons intrinsic to the SENC. The function of the SENC is unknown, but it may be involved in regulatory processes in which CSF oxytocin has been implicated, such as osmotic homeostasis and/or cardiovascular reflexes.
Animals↗
How to structure clinical practice guidelines for continuous quality improvement?
The purpose of this study was to evaluate the relevance of available practice guidelines to clinical quality improvement programs. A sample of 19 guidelines was evaluated in four prominent primary care areas. Two research assistants independently coded the clinical conditions and recommended/not recommended procedures abstracted from the guidelines (Cohen's kappa .67 and .50, respectively). An average of 35.1 (+/- 25.8) medical conditions and 48.4 (+/- 41.5) clinical procedures were defined by the guidelines. Most conditions were defined by using ICD-9-CM, age/sex group, or therapy, but 29% of definitions included symptoms which are not coded routinely. CPT codes alone were unable to identify most procedures. AHCPR guidelines mentioned significantly more procedures (p < .001) and fewer symptoms (p < .001) per clinical condition than other guidelines. The difficulty of finding codes for conditions and procedures, the high rate of non-codable items, and the lack of recommended measures limit the applicability of published clinical practice guidelines to continuous quality improvement programs.
Age Factors↗
The J. Otto Lottes Health Sciences Library and the Microcomputer Learning Laboratory.
Opened in 1985, the J. Otto Lottes Health Sciences Library at the University of Missouri-Columbia has adapted to changes in information technology by installing a fiber optic backbone, establishing local area networks and file servers with databases and software programs, establishing a microcomputer learning laboratory, and responding to the needs of a problem-based learning curriculum. The library works cooperatively with the Medical Informatics Group, which is housed in the library and runs the micro laboratory, to support student and faculty computing.
CD-ROM↗
Intrauterine oxygen tension during the oestrous cycle in the hamster: patterns of change.
Oxygen tension (pO2) within the uterine lumen of the hamster during the oestrous cycle was measured in vivo with a polarographic oxygen sensor. Mean oxygen tension underwent cyclic variation; maximum pO2 occurred during dioestrus (35.2 +/- 1.9 mmHg). Minute-to-minute alterations in pO2 also occurred; the frequency of change in pO2 was maximal during early dioestrus (94.4 +/- 8.9 peaks/hr) and minimal during pro-oestrus (31.2 +/- 5.6 peaks/hr). The amplitude of change in pO2 was maximal during late dioestrus (40.7 +/- 3.6 mmHg) and minimal during pro-oestrus (5.1 +/- 1.2 mmHg). Thus, intrauterine pO2 increases during periods of progesterone dominance and decreases under oestrogenic stimulation. Arterial and venous pO2 were 89.9 +/- 4.8 and 38.9 +/- 1.8 mmHg, respectively. Thus, mean intrauterine pO2 was consistently less than venous blood levels and varied as much as 30 mmHg during the oestrous cycle. The level of pO2 prevailing during the interval of the cycle in which insemination is permitted is intermediate to the maximum and minimum levels occurring during the oestrous cycle and is clearly sufficient to meet the metabolic requirements of spermatozoa during their passage through the uterus.
Animals↗
Effects of cyclic GMP on smooth muscle relaxation.
Cyclic GMP levels within smooth muscle are affected then by a number of different pathways. Physiologically NO and ANF are probably the two most important regulators for smooth muscle function, but a variety of other mediators and pharmacological agents may also influence this system. Because of the important role that cyclic GMP plays in the control of smooth muscle tone, which clearly includes vascular smooth muscle, it is now and will continue to be in the future an important physiological and biochemical target for research and a pharmacological target for therapeutic agents.
Animals↗
Cyclo-oxygenase and nitric oxide synthase isoforms in rat carrageenin-induced pleurisy.
1. The profiles of cyclo-oxygenase (COX) and nitric oxide synthase (NOS) isoforms were determined in the rat carrageenin-induced pleurisy model of acute inflammation. 2. The enzymes were assessed in peripheral blood leucocyte (PBL) cell pellets taken from untreated animals and at 2, 6 and 24 h after injection of the irritant in pleural exudate cell pellets and lung homogenates. 3. COX activity was assessed by the generation of prostacyclin (PGI2, measured as the stable metabolite, 6-keto prostaglandin F1 alpha) and prostaglandin E2 (PGE2). Western blot analysis and immunohistochemistry were also carried out. 4. NOS activity was based on the conversion of [3H]-L-arginine to [3H]-L-citrulline in the presence (total NOS activity) or absence of Ca2+ (inducible NOS; iNOS). 5. Peripheral blood leucocyte samples contained low levels of COX activity. In pleural exudate cell pellets, COX activity peaked at 2 to 6 h after injection of the carrageenin. At 24 h, COX activity was significantly reduced. 6. Western blot analysis demonstrated that the inducible isoform of COX (COX-2), was the predominant enzyme at all time points. Low levels of COX-2 were seen in PBLs. In pleural exudate cell pellets maximal COX-2 protein levels were seen at 2 h. 7. Immunohistochemistry confirmed the findings of Western blot studies. Approximately 10% of polymorphonuclear neutrophils (PMNs) in PBLs from untreated animals were immunopositive for COX-2. In cell pellet smears from carrageenin-induced pleurisy taken 2 h after injection of the irritant, PMNs were also the major source of COX-2 immunoreactivity. A small proportion of macrophages and mesothelial cells were also immunolabelled for COX-2.8. Low levels of NOS activity were seen in PBLs. In pleural exudates NOS activity was maximum at 6 h and greatly reduced by 24 h. This activity was solely attributable to iNOS.9. The present results illustrated a similar profile of COX and NOS activity in the carrageenin-induced pleurisy model of acute inflammation. It was demonstrated that COX-2 and iNOS were the predominant isoforms of their respective enzymes.
6-Ketoprostaglandin F1 alpha↗
Induction of cyclo-oxygenase-2 by cytokines in human pulmonary epithelial cells: regulation by dexamethasone.
1. Cyclo-oxygenase metabolizes arachidonic acid to prostaglandin H2 (PGH2) and exists in at least two isoforms. Cyclo-oxygenase-1 (COX-1) is expressed constitutively whereas COX-2 is induced by lipopolysaccharide (LPS) and some cytokines in vitro and at the site of inflammation in vivo. Epithelial cells may be an important source of prostaglandins in the airways and we have, therefore, investigated the expression of COX-1 or COX-2 isoforms in primary cultures of human airway epithelial cells or in a human pulmonary epithelial cell line (A549). 2. COX-1 or COX-2 protein was measured by western blot analysis using specific antibodies to COX-2 and selective antibodies to COX-1. The activity of COX was assessed by the conversion of either endogenous or exogenous arachidonic acid to four metabolites, PGE2, PGF2 alpha, thromboxane B2 or 6-oxo PGF1 alpha measured by radioimmunoassay. Thus, COX-1 or COX-2 activity was measured under two conditions; initially the accumulation of the COX metabolites formed from endogenous arachidonic acid was measured after 24 h. In other experiments designed to measure COX activity directly, cells were treated with cytokines for 12h before fresh culture medium was added containing exogenous arachidonic acid (30 microM) for 15 min after which COX metabolites were measured. 3. Untreated primary cells or A549 cells contained low amounts of COX-1 or COX-2 protein. Bacterial LPS (1 micro g ml-1 for 24 h) induced COX-2 protein in the primary cells, a process which was enhanced by interferon-gamma, with no further increase in the presence of a mixture of cytokines (interleukin-1 beta, tumour necrosis factor-alpha and interferon-gamma, 10 ng ml-1 for all). In contrast, A549 cells contained only low levels of COX-2 protein after exposure to LPS or LPS plus interferon-y, but contained large amounts of COX-2 protein after exposure to the mixture of cytokines.4. Untreated human pulmonary primary cells or A549 cells released low levels of all COX metabolites measured over a 24 h incubation period. This release was enhanced by treatment of either cell type with the mixture of cytokines (interleukin-1 beta , tumour necrosis factors- and interferon-gamma, 10 ng ml-1 for all).PGE2 was the principal COX metabolite released by cytokine-activated epithelial cells. The release of PGE2 induced by cytokines occurred after a lag period of more than 6 h.5. The glucocorticosteroid, dexamethasone (1 micro M; 30 min prior to cytokines) completely suppressed the cytokine-induced expression of COX-2 protein and activity in both primary cells and A549 cells.6. In experiments where COX-2 activity was supported by endogenous stores of arachidonic acid,treatment of A549 cells with interleukin-l beta but not tumour necrosis factor a or interferon-gamma alone caused a similar release of PGE 2 to that seen when the cytokines were given in combination. However, both interleukin-l beta and necrosis factor- alone produced similar increases in COX-2 activity (measured in the presence of exogenous arachidonic acid) as seen when the mixture of interleukin-l beta, tumour necrosis factor- alpha and interferon-gamma were used to stimulate the cells.7. These findings show that COX-2 expression correlates with the exaggerated release of prostaglandins from cytokine-activated human pulmonary epithelial cells and that the induction of the enzyme is suppressed by a glucocorticosteroid. These findings may be relevant to inflammatory diseases of the lung, such as asthma.
Arachidonic Acid↗