Objectives: Catecholamine-mediated stress responses are associated with decreased cellular immune resistance to infection such as periodontal diseases and recurrent herpes simplex virus. Using a murine model we have previously shown that norepinephrine causes decreased T-lineage cell expression of Thy-1 mRNA through a b-adrenergic/cAMP/protein kinase A-dependent mechanism (J. Immunol. 161:4825-4833) which is likely to be associated with a generic mRNA decay system critical to immune regulation. Methods: Here we report that utilizing UV cross-linking and riboprobe transfer assays, multiple mouse S49 lymphosarcoma cytoplasmic proteins bind similar ARE destabilization target base regions of the 3'UTR of mRNAs of TNFa, the b-adrenergic receptor and the cell surface T cell activation protein Thy-1 in a catecholamine/cAMP-enhanced manner. Results: Proteins of 40-50kDa were shown by Western blotting and immunoprecipitation to be murine isoforms of the classic ARE-binding mRNA destabilizing protein AUF-1. Levels of AUF-1 mRNA and immunoreactive cytoplasmic AUF-1 protein are elevated 2-3 fold and 1.2-1.5 fold respectively in response to 8Br cAMP in wild type S49, but not in protein kinase A-deficient S49 cells. cAMP also leads to increases in cytoplasmic versus nuclear ARE-binding activity of multiple Thy-1 ARE binding proteins, including AUF-1. Conclusions: Our data suggest that these 3'mRNA sequences are a functional equivalent to classic cytokine, receptor and oncogene AREs, and are consistent with the hypothesis that catecholamine/cAMP/protein kinase A-mediated increases in these binding proteins play a role in stress-associated acceleration of T cell mRNA decay.

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