Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Meconium aspiration causes intensive inflammatory reactions in the lungs, and may lead to neonatal respiratory disorder. Infiltrated inflammatory cells, particularly macrophages, play an important role in such an inflammation. A rat alveolar macrophage cell line (ATCC8383) was exposed to meconium alone or in combination with dexamethasone, budesonide, or interferon-gamma. Nitric oxide (NO) accumulation in the supernatant of the cell culture was detected by Griess reaction, and mRNA of inducible NO synthase (iNOS) expression was detected by reverse transcriptase-PCR. Nuclear factor-kappa B was analyzed by electrophoretic mobility shift assay, and iNOS location and nuclear factor-kappa B transactivation were determined by immunostaining. Our results showed that meconium was capable of inducing production of NO and expression of iNOS in alveolar macrophages in a dose- (1-25 mg/mL, p < 0.05) and time- (4-48 h, p < 0.05) dependent manner. This capability of meconium could be further enhanced in the presence of interferon-gamma (100 IU/mL, p < 0.05). Budesonide (10(-4)-10(-10) M) or dexamethasone (10(-4)-10(-6) M) effectively inhibited the meconium-induced NO production (p < 0.05). Using the protein synthesis inhibitor cycloheximide, we demonstrated that meconium directly induced iNOS in macrophages. Furthermore, meconium also triggered nuclear factor-kappa B activation, a mechanism possibly responsible for the iNOS expression. Our findings suggest that meconium is a potent inflammatory stimulus, resulting in iNOS expression, leading to overproduction of NO from the macrophages, which may be of pathogenic importance in meconium aspiration syndrome. In vitro steroids down-regulated the iNOS expression, thus suggesting a potential to down-regulate NO-mediated inflammation in neonates with meconium aspiration syndrome.
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PMID:Meconium induces expression of inducible NO synthase and activation of NF-kappaB in rat alveolar macrophages. 1138 44

Endotoxin, tumor necrosis factor (TNF), and organic dust constitute proinflammatory stimuli involved in the initiation of inflammation. The major receptor for endotoxin (lipopolysaccharide [LPS]) is Toll-like receptor 4 (TLR4), whereas TLR2 binds to agents from gram-positive bacteria. The aim of the study was to elucidate whether TLR2 and TLR4, expressed on primary bronchial epithelial cells (PBECs), are influenced by exogenous (organic dust and LPS) and endogenous (TNF) stimuli and whether this interaction is influenced by a glucocorticosteroid. The cells were exposed to LPS (10 microg/ml), TNF (10 ng/ml), or dust (100 microg/ml) 1.5 and 6 h, in the presence or absence of budesonide (10(-6) M) in vitro. The mRNA expression of interleukin (IL)-6, IL-8, TLR2, and TLR4 were measured with real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and IL-6 and IL-8 release was assessed with enzyme-linked immunosorbent assay (ELISA). To elucidate the importance of TLR-signaling for IL-6 and IL-8 secretion, the effect of TLR-blockers was studied. Endotoxin, TNF, and dust stimulated the release of IL-6 and IL-8 in a time-dependent manner. Budesonide significantly attenuated the release and expression of IL-6 and IL-8 after exposure. Budesonide did not influence TLR expression, but costimulation with LPS, TNF, or dust together with budesonide increased TLR2 expression synergistically. Blocking of TLR2 and TLR4 reduced cytokine secretion in stimulated cells. Budesonide reduced IL-6 and IL-8 production and enhanced expression of TLR2 in PBECs only in the presence of a proinflammatory stimulus. These findings contribute to our understanding of the beneficial effects of glucocorticosteroids during chronic obstructive pulmonary disease (COPD) exacerbations and asthma, which are frequently caused by microorganisms.
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PMID:Budesonide enhances Toll-like receptor 2 expression in activated bronchial epithelial cells. 2038 3