Absence of the cell cycle inhibitor p21Cip1 reduces LPS-induced NO release and activation of the transcription factor NF-kappaB in mixed glial cultures.
We have studied possible differences in glial activation between cells from wild-type and p21Cip1-/- mice. We compared the effect of serum mitogenic stimulation on proliferation rate and on the total number of glial cells after 7 days of culture. No differences between wild-type and p21Cip1-/- glial cells were observed. We also compared the effect of lipopolysaccharide (LPS) from Escherichia coli, an agent widely used to induce glial activation. Nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) release, and nuclear factor kappa-B (NF-kappaB) activation were evaluated as indicators of glial activation. We observed an attenuation of NO release and NF-kappaB activation in p21Cip1-/- glial cells when compared with glial cells from wild-type mice. In contrast, TNF-alpha release was enhanced in p21Cip1-/- glia. These results suggest that the cell cycle inhibitor p21Cip1 plays a role in the inflammatory response induced by LPS.
Tusell
Josep Maria
JM
Department of Neurochemistry, Institut d'Investigacions Biomèdiques de Barcelona, IIBB-CSIC, IDIBAPS, Barcelona, Spain.
Saura
Josep
J
Serratosa
Joan
J
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D050759:Cyclin-Dependent Kinase Inhibitor p21; D015536:Down-Regulation / Q000235:genetics; D004660:Encephalitis / Q000235:genetics* / Q000378:metabolism; D005911:Gliosis / Q000235:genetics* / Q000378:metabolism; D008070:Lipopolysaccharides; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
C493957:Cdkn1a protein, mouse; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide