Abstract

In order to understand the molecular regulation of the acute phase response, we have isolated human cDNA specific for C reactive protein. Utilizing this cDNA as a probe and mRNA translation systems, we will study the synthesis and post-synthetic processing of CRP, determine the structure of the RP gene ad its 5' flanking region, and study the level of induction of rabbit CRP gene expression (transcription, translation, post synthetic) following an acute phase stimulus. Similar studies will be undertaken for serum amyloid P (SAP) and utilizing Syrian hamsters to elucidate the structures and mechanisms responsible for hormonal and acute phase induction of the CRP/SAP like gene in this species. Finally, studies of the evolution of this gene will be undertaken. These results of those studies should have importance not only for acute phase proteins and the inflammatory response, but also provide insights into genetic and acquired disorders of plasma protein synthesis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI020959-01A1
Application #
3130836
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1984-12-01
Project End
1987-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code

  Publications

Webb, C F; Tucker, P W; Dowton, S B (1989) Expression and sequence analyses of serum amyloid A in the Syrian hamster. Biochemistry 28:4785-90
Falus, A; Beuscher, H U; Auerbach, H S et al. (1987) Constitutive and IL 1-regulated murine complement gene expression is strain and tissue specific. J Immunol 138:856-60
Miura, N; Prentice, H L; Schneider, P M et al. (1987) Synthesis and regulation of the two human complement C4 genes in stable transfected mouse fibroblasts. J Biol Chem 262:7298-305
Floyd-Smith, G; Whitehead, A S; Colten, H R et al. (1986) The human C-reactive protein gene (CRP) and serum amyloid P component gene (APCS) are located on the proximal long arm of chromosome 1. Immunogenetics 24:171-6
Perlmutter, D H; Dinarello, C A; Punsal, P I et al. (1986) Cachectin/tumor necrosis factor regulates hepatic acute-phase gene expression. J Clin Invest 78:1349-54
Takemura, S; Rossing, T H; Perlmutter, D H (1986) A lymphokine regulates expression of alpha-1-proteinase inhibitor in human monocytes and macrophages. J Clin Invest 77:1207-13
Mantzouranis, E C; Dowton, S B; Whitehead, A S et al. (1985) Human serum amyloid P component. cDNA isolation, complete sequence of pre-serum amyloid P component, and localization of the gene to chromosome 1. J Biol Chem 260:7752-6
Dowton, S B; Woods, D E; Mantzouranis, E C et al. (1985) Syrian hamster female protein: analysis of female protein primary structure and gene expression. Science 228:1206-8
Woo, P; Korenberg, J R; Whitehead, A S (1985) Characterization of genomic and complementary DNA sequence of human C-reactive protein, and comparison with the complementary DNA sequence of serum amyloid P component. J Biol Chem 260:13384-8
Ramadori, G; Sipe, J D; Colten, H R (1985) Expression and regulation of the murine serum amyloid A (SAA) gene in extrahepatic sites. J Immunol 135:3645-7

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