Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

All-trans retinoic acid (ATRA) is a potent retinoid, which has been used successfully in different clinical settings as a potential drug to treat COPD and emphysema. In the present study, we analyzed genes modulated by ATRA by performing mRNA expression array analysis on alveolar macrophages after treatment with ATRA. Here we observed a 375-fold up-regulation of Prostaglandin-E Synthase (microsomal PGES-1, NM_004878 PTGES) which mediates the conversion of prostaglandin H(2) (PGH(2)) to Prostaglandin E(2) (PGE(2)). We furthermore studied the expression of PTGES after treatment with ATRA in human monocyte-derived macrophages (MDMs) and bronchoalveolar lavage (BAL) cells. ATRA up-regulated PTGES mRNA expression in MDMs generated with M-CSF by 2500-fold whereas in M-CSF+IL-13 macrophages the up-regulation was only 20-fold. Similarly, ATRA up-regulated PTGES mRNA expression by factor 1524 in BAL cells. The up-regulation of PTGES mRNA expression by ATRA is both time and dose dependent. IL-13 suppressed the ATRA induced PTGES expression at both mRNA and protein level in MDM and BAL cells. We also observed that LPS acts synergistically with ATRA in MDMs and strongly induces PTGES expression. ATRA had little impact on cyclooxygenase-1 and -2 (COX-1 and -2) expression as compared to PTGES expression under the same experimental conditions. Furthermore, we observed an induction of PGE(2) levels by ATRA in BAL cells. These data indicate that ATRA is a potent inducer of PTGES expression in human macrophages but not in alternatively activated macrophages and suggest that the eicosanoid pathway is important for ATRA action in macrophages.
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PMID:All-trans retinoic acid up-regulates Prostaglandin-E Synthase expression in human macrophages. 2220 20

Chronic inflammation plays a crucial role in cigarette smoke-related carcinogenesis. Accordingly, anti-inflammatory agents, such as nonsteroidal anti-inflammatory drugs (NSAIDs), provide a rational strategy in cancer chemoprevention. We assayed celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, and licofelone, an inhibitor of COX-1, COX-2, and 5- lipoxygenase (5-LOX), for the ability to modulate carcinogenesis in neonatal mice exposed to mainstream cigarette smoke (MCS) for 4 months and thereafter kept in filtered air for 3.5 months. A preliminary toxicity study and a chemoprevention study involved the use of 591 Swiss H mice. Exposure to MCS caused a variety of pulmonary emphysema, alveolar and bronchial epithelial hyperplasias, proliferation of blood vessels, microadenomas, adenomas and malignant tumors, as well as kidney tubular and urinary bladder papillary epithelial hyperplasias. Celecoxib (1600 mg/kg diet) and even better licofelone (960 mg/kg diet) were able to significantly attenuate the MCS-induced alterations of inflammatory nature, including pulmonary emphysema, alveolar epithelial hyperplasias and microadenomas and urinary tract hyperplastic lesions when given to mice according to a protocol that mimics an intervention in current smokers. Moreover, celecoxib attenuated the yield of lung adenomas and both NSAIDs showed some involvement in lowering the progression to cancer in the lung. Celecoxib exhibited some protective effects even when given according to a protocol involving its administration after discontinuation of exposure to MCS. However, both agents and especially celecoxib showed some hepatotoxicity and affected survival and body weight gain of mice when administered to MCS-exposed mice in the long term.
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PMID:Modulation by licofelone and celecoxib of experimentally induced cancer and preneoplastic lesions in mice exposed to cigarette smoke. 2568 74