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Quantification of PPAR-γ protein in monocyte/macrophages from healthy smokers and non-smokers: A possible direct effect of nicotine
- Source :
- Life Sciences. 81:906-915
- Publication Year :
- 2007
- Publisher :
- Elsevier BV, 2007.
-
Abstract
- Previous observations demonstrated that Peroxisome Proliferator-Activated Receptor-gamma (PPAR-gamma), a key regulator of adipocyte differentiation, is expressed in a large variety of cells, including cells of the monocyte/macrophage lineage. This study was aimed to quantify both the constitutive and ligand-induced PPAR-gamma expression in monocytes and monocyte-derived macrophages (MDM) isolated from healthy smokers and non-smokers, and to evaluate the possible direct effect of nicotine. PPAR-gamma protein was detected by Western blot and quantification was performed by calculating the ratio between PPAR-gamma and beta-actin protein expression. Cytokine release was measured with enzyme-linked immunoassay kits. Constitutive PPAR-gamma protein was detected in human monocytes and its expression was up-regulated along with differentiation to MDM. The endogenous ligand 15-deoxy-delta(12,14)-prostaglandin J(2) and the synthetic agonist ciglitazone enhanced PPAR-gamma expression, the former being effective also at low micromolar concentrations. Both agonists significantly inhibited the basal secretion of pro-inflammatory cytokines (e.g., TNF-alpha, IL-6), ciglitazone being more potent. Monocytes and MDM from healthy smokers presented a significantly enhanced (4-fold and 2.5-fold, respectively) constitutive PPAR-gamma expression, as compared to those from healthy non-smokers. However, ligand-induced PPAR-gamma expression and inhibition of cytokine secretion were similar in healthy smokers and non-smokers. Nicotine dose-dependently enhanced PPAR-gamma expression with a maximum at 10 muM, and inhibited release of pro-inflammatory cytokines; these effects were reversed by alpha-bungarotoxin. Nicotine and PPAR-gamma agonists did not exert synergistic effects. In conclusion, monocytes and MDM from healthy smokers present a constitutively enhanced PPAR-gamma expression; this effect is reproduced, to some extent, by nicotine in vitro.
- Subjects :
- Adult
Male
Nicotine
medicine.medical_specialty
alpha7 Nicotinic Acetylcholine Receptor
medicine.medical_treatment
Receptors, Nicotinic
Gene Expression Regulation, Enzymologic
Monocytes
General Biochemistry, Genetics and Molecular Biology
Ciglitazone
Internal medicine
medicine
Humans
Macrophage
General Pharmacology, Toxicology and Pharmaceutics
Interleukin 6
biology
Interleukin-6
Tumor Necrosis Factor-alpha
Macrophages
Monocyte
Smoking
General Medicine
Actins
Up-Regulation
PPAR gamma
Endocrinology
medicine.anatomical_structure
Cytokine
biology.protein
Female
Thiazolidinediones
Cytokine secretion
Tumor necrosis factor alpha
medicine.drug
Subjects
Details
- ISSN :
- 00243205
- Volume :
- 81
- Database :
- OpenAIRE
- Journal :
- Life Sciences
- Accession number :
- edsair.doi.dedup.....a0236b7f7f9d54adabe1e0531581a4f4