Aging increases murine macrophage (M<|>) cyclooxygenase (COX-2) mRNA expression

We previously showed that Mφ from old mice have higher PGE2 production and COX activity compared to young mice. This age-associated increase in PGE2 production contributes to decline in T cell proliferation with aging. The present study was conducted to determine the mechanism of age-associated increase in Mφ COX activity. Of the two COX isoforms identified, COX-1 (PGHS-1) is constitutively expressed in nearly all cells, the second, COX-2 (PGHS-2) is induced by a wide range of ligands. We compared levels of COX-1 and COX-2 mRNA prepared from peritoneal resident Mφ of young (5 mo) and old (22 mo) C57BL/6NIA mice. Adherent Mφ, pooled from 18-36 mice for final n=3, were stimulated with lipopolysaccharide (LPS) for 0, 2, 6, 8, 12, and 18 h. Total RNA was isolated and levels of COX-1 and COX-2 were measured by RNase protection assay. COX-1 mRNA was not detectable under these conditions. Maximum expression of COX-2 was observed at 2 h in both young and old Mφ. Mφ from old mice had higher mRNA level at 2, 4, H and 12 hrs compared to young mice. Statistically significant differences, however, were observed at 2 h (p<0.05). It is concluded that ageassociated increase in PGE2 production is in part due to higher expression of COX-2 mRNA. These findings have significant implications for ageassociated immune and inflammatory dysregulations.