Persistent expression of serum amyloid A during experimentally induced chronic inflammatory condition in rabbit involves differential activation of SAF, NF-kappa B, and C/EBP transcription factors.
The serum amyloid A (SAA) protein has been implicated in the pathogenesis of several chronic inflammatory diseases. Its induction mechanism in response to a chronic inflammatory condition was investigated in rabbits following multiple s.c. injections of AgNO3 over a period of 35 days. During unremitting exposure to inflammatory stimulus, a persistently higher than normal level of SAA2 expression was seen in multiple tissues. Induction of SAA was correlated with higher levels of several transcription factor activities. Increased SAA-activating factor (SAF) activity was detected in the liver, lung, and brain tissues under both acute and chronic inflammatory conditions. In the heart, kidney, and skeletal muscle tissues, this activity remained virtually constant. In contrast, CCAAT enhancer binding protein (C/EBP) DNA-binding activity was transiently induced in selective tissues. Higher than normal NF-kappa B DNA-binding activity was detected in the lung and to a lesser extent in the liver and kidney tissues under both acute and chronic conditions. This result suggested that C/EBP, SAF, and NF-kappa B are required for transient acute phase induction of SAA whereas SAF and NF-kappa B activities are necessary for persistent SAA expression during chronic inflammatory conditions.
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Department of Veterinary Pathobiology, University of Missouri, Columbia 65211, USA. rayal@missouri.edu
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D000208:Acute Disease; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D002908:Chronic Disease; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D004742:Enhancer Elements, Genetic / Q000276:immunology; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism*; D007279:Injections, Subcutaneous; D016328:NF-kappa B / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism* / Q000502:physiology; D009928:Organ Specificity / Q000276:immunology; D011817:Rabbits; D000685:Serum Amyloid A Protein / Q000096:biosynthesis*; D012835:Silver Nitrate / Q000008:administration & dosage; D014157:Transcription Factors / Q000502:physiology
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D000685:Serum Amyloid A Protein; D014157:Transcription Factors; C076035:c-MYC-associated zinc finger protein; D012835:Silver Nitrate