title: Age-associated alterations in splenic iNOS regulation: influence of constitutively expressed IFN-gamma and correction following supplementation with PPARalpha activators or vitamin E.
abstract: Alterations in transcription factor activities in aged mice may lead to the production of many inflammatory molecules in the absence of exogenous stimulation. Splenocytes from 22-month-old female C57BL/6 mice are dysregulated in their capacity to control the inducible nitric oxide synthase gene as a result of elevations in the endogenous levels and activity of interferon (IFN)-gamma. Splenocytes from aged mice produced high levels of IFN-gamma in vitro and active STAT-1 was found in nuclear extracts from these splenocytes. Administration to aged mice of neutralizing antibodies against IFN-gamma imposed appropriate regulation over nitric oxide production by stimulated splenocytes. Reestablishment of normal redox balance following dietary supplementation of aged mice with activators of the peroxisome proliferator-activated receptor alpha or the antioxidant alpha-tocopherol (vitamin E) restored appropriate regulation over both the production of IFN-gamma and the secretion of nitric oxide.
authors.affiliation: Department of Pathology, University of Utah, Salt Lake City, Utah 84132, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Poynter
authors.forename: R A
authors.initials: RA
authors.lastname: Daynes
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D000906:Antibodies / Q000276:immunology; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism / Q000652:urine; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D010084:Oxidation-Reduction; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000502:physiology; D050794:STAT1 Transcription Factor; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000819:agonists* / Q000502:physiology; D014810:Vitamin E / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000906:Antibodies; D004268:DNA-Binding Proteins; D008070:Lipopolysaccharides; D011743:Pyrimidines; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D014810:Vitamin E; D009569:Nitric Oxide; D007371:Interferon-gamma; C006253:pirinixic acid; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse