Upregulation of p21Cip1 in activated glial cells

Abstract

The cdk inhibitor p21Cip1, also named p21Cip1/Waf1, is intimately involved in coupling growth arrest to cellular differentiation in several cell types. p21Cip1 is a multifunctional protein that might regulate cell-cycle progression at different levels. In a recent study, we found no differences in the rate of proliferation between glial cells from wild-type and p21Cip1−/− mice. In the present study, we examined differences in glial activation between glial cells from wild-type and p21Cip1−/− mice, using mixed glial cultures, microglia-enriched cultures, and astrocyte-enriched cultures. We compared the effect of lipopolysaccharide and two forms (oligomeric and fibrillar) of the 1-42 β-amyloid peptide on glial activation. We observed an attenuation of nuclear translocation of the nuclear factor kappa-B in p21Cip1−/− glial cells, when compared with glial cells from wild-type mice. In contrast, tumor necrosis factor-α release was enhanced in p21Cip1−/−microglial cells. In addition glial activation induced by lipopolysaccharide and the fibrillar form of the 1-42 β-amyloid peptide upregulated p21Cip1. Our results support a role for p21Cip1 in the activation of glial cells, particularly in microglia.