The TNF-α, IL-1-β, IL-6, IL-8, INF-γ, PGE-2 and IL-10 Expression in Meconium Aspirated Newborn Lungs

Vidyasagar, Dharmapuri; Bhat, Rama; Uhal, Bruce D.; Navale, Shan; Zagariya, Alexander

doi:10.1203/00006450-199904020-01933

Cited by 2 publications

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“…Human meconium itself appears to have some neutrophil chemotactic activity, presumably due to the presence of potently chemotactic cytokines, such as IL-8 (24). Aspirated meconium may further induce intrapulmonary production of proinflammatory cytokines and prostaglandins (25,26). Our results however indicate that alveolar TNF-␣ release is not significantly increased in the meconium-contaminated lungs.…”

Section: Discussioncontrasting

confidence: 54%

“…Thus, although TNF-␣ is a potent activator of neutrophils and 195 may up-regulate neutrophil/endothelial adhesion receptors, it is probably not markedly responsible for the early local extravasation and accumulation of leukocytes within the alveolar spaces (8,12). Previous experimental data indeed suggest that pulmonary TNF-␣ synthesis and release is time-dependent and peaks only at 24 h after meconium insult (25). A bulk of clinical and experimental evidence indicates that neutrophils, when stimulated, are involved in the pathogenesis of the acute lung injury of various origin (8).…”

Section: Discussionmentioning

confidence: 94%

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Meconium Induces Only Localized Inflammatory Lung Injury in Piglets

et al. 2003

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Section: Discussioncontrasting

confidence: 54%

Section: Discussionmentioning

confidence: 94%

Meconium Induces Only Localized Inflammatory Lung Injury in Piglets

et al. 2003

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“…Studies in rats (19) and humans (9) indicate that lipopolysaccharidestimulated alveolar macrophages can release inflammatory and vasoactive prostaglandins. Accordingly, in lungs with meconium contamination, increased prostaglandin E 2 and thromboxane A 2 formation has been found (20,21). Corroborating our present results, this stimulated prostaglandin production seems to be due to up-regulation of COX-2 in macrophages, the predominant inflammatory cells in the alveoli (9).…”

Section: Discussionsupporting

confidence: 74%

Meconium Aspiration Stimulates Cyclooxygenase-2 and Nitric Oxide Synthase-2 Expression in Rat Lungs

2003

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To study the impact of meconium aspiration on the biosynthesis of prostaglandins and nitric oxide, we investigated the effects of intratracheal meconium instillation on the expression of cyclooxygenase-1 (COX-1) and -2 (COX-2) and endothelial (NOS-3) and inducible (NOS-2) nitric oxide synthase in rat lungs. Anesthetized, tracheotomized, and ventilated rats received 3 mL/kg human meconium suspension intratracheally (n ϭ 19), and 14 control rats received an equal volume of saline. Ten rats were pretreated with indomethacin, and 13 rats were pretreated with dexamethasone. The lungs were ventilated with 70% oxygen for 3 h after the insult, and the level of COX-1, COX-2, NOS-2, and NOS-3 mRNA in lung tissue was analyzed by Northern blot hybridization. Furthermore, the expression and localization of the enzyme proteins was analyzed by immunohistochemistry. COX-1 and NOS-3 were clearly expressed in the lungs of control rats, whereas the level of COX-2 and NOS-2 expression was minimal. Meconium administration did not affect the expression of COX-1, but COX-2 expression was upregulated in the respiratory epithelium and alveolar macrophages. Meconium also induced up-regulation of NOS-2 in the pulmonary epithelium, vascular endothelium, and macrophages. Indomethacin pretreatment did not affect the enzyme expressions, whereas dexamethasone administration significantly inhibited the meconium-induced COX-2 and NOS-2 up-regulation. Our data thus indicate that intrapulmonary meconium upregulates lung COX-2 and NOS-2 gene expression, suggesting an important role for prostaglandins and nitric oxide in the meconium aspiration-induced pulmonary inflammation and hemodynamic changes. Aspiration of meconium frequently causes a severe neonatal disorder, characterized by initial airway obstruction with subsequent alveolocapillary injury and ventilation/perfusion mismatching in the lungs (1). In a few hours, the initial insult is followed by an inflammatory reaction in the lungs with neutrophil accumulation and concomitant increase in the pulmonary vascular resistance (1-4). The pathogenetic mechanisms of these alterations are still unclear, although the stimulation in the production of bioactive mediators in alveolar macrophages has been proposed (4 -6).Prostaglandins have been implicated as important modulators of various pathologic inflammatory and cardiovascular processes. The rate-limiting step in prostaglandin biosynthesis is the conversion of arachidonic acid to endoperoxides by cyclooxygenase enzymes, known to exist in two isoforms (7). The constitutive cyclooxygenase-1 (COX-1) is ubiquitously expressed and enrolled in physiologic processes, whereas the low basal activity of cyclooxygenase-2 (COX-2) can be stimulated by endogenous and exogenous mediators (7,8). Accordingly, COX-2 is activated in endotoxin and cytokinestimulated alveolar macrophages and pulmonary epithelial cells in vitro and this will result in the generation of large amounts of prostaglandin E 2 (8 -10). The activity of pulmonary prostaglandin synthesis after as...

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The TNF-α, IL-1-β, IL-6, IL-8, INF-γ, PGE-2 and IL-10 Expression in Meconium Aspirated Newborn Lungs

Cited by 2 publications

References 0 publications

Meconium Induces Only Localized Inflammatory Lung Injury in Piglets

Meconium Induces Only Localized Inflammatory Lung Injury in Piglets

Meconium Aspiration Stimulates Cyclooxygenase-2 and Nitric Oxide Synthase-2 Expression in Rat Lungs

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