Upregulation of p21Cip1 in activated glial cells.
The cdk inhibitor p21(Cip1), also named p21(Cip1/Waf1), is intimately involved in coupling growth arrest to cellular differentiation in several cell types. p21(Cip1) 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 p21(Cip1-/-) mice. In the present study, we examined differences in glial activation between glial cells from wild-type and p21(Cip1-/-) 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 beta-amyloid peptide on glial activation. We observed an attenuation of nuclear translocation of the nuclear factor kappa-B in p21(Cip1-/-) glial cells, when compared with glial cells from wild-type mice. In contrast, tumor necrosis factor-alpha release was enhanced in p21(Cip1-/-)microglial cells. In addition glial activation induced by lipopolysaccharide and the fibrillar form of the 1-42 beta-amyloid peptide upregulated p21(Cip1). Our results support a role for p21(Cip1) in the activation of glial cells, particularly in microglia.
Tusell
Josep Maria
JM
Department of Cerebral Ischemia and Neurodegeneration, IIBB-CSIC, IDIBAPS, Rosselló 161, Barcelona, Spain.
Ejarque-Ortiz
Aroa
A
Mancera
Pilar
P
Solà
Carme
C
Saura
Josep
J
Serratosa
Joan
J
D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D015870:Gene Expression; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D009457:Neuroglia / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
D016229:Amyloid beta-Peptides; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010446:Peptide Fragments; D012333:RNA, Messenger; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C075222:amyloid beta-protein (1-42)