TY - JOUR
T1 - Interferon γ induces the expression of p21(waf-1) and arrests macrophage cell cycle, preventing induction of apoptosis
AU - Xaus, Jordi
AU - Cardó, Marina
AU - Valledor, Annabel F.
AU - Soler, Concepció
AU - Lloberas, Jorge
AU - Celada, Antonio
N1 - Funding Information:
We thank Joan Massagué from the Sloan Kettering Institute, New York; Ramon Merino, University of Cantabria, Santander, Spain; Oriol Bach, University of Barcelona, Spain; and Gerard Evan, ICRF, London, UK, for the gift of several reagents. We are also grateful to Philip Leder, Harvard Medical School (HHMI), Boston, MA, for the generous gift of the p21 waf-1 KO mice. We specially thank Gabriel Gil, Institut Municipal d'Investigacions Mediques, Barcelona, for his help with the p21 waf-1 KO mice, cdk2 kinase assays, and for discussions and critical reading of the manuscript. We acknowledge the help received from Jaume Comas and Rosario González from the flow cytometry facility of the Serveis Científico Tècnics de la Universitat de Barcelona. We also acknowledge the editorial assistance of Martin Cullel-Young. This work was supported by grants from the Comision Interministerial de Ciencia y Tecnologia (SAF98/0102 and PM 98/0200) to A. C.
PY - 1999/7
Y1 - 1999/7
N2 - Incubation of bone marrow macrophages with lipopolysaccharide (LPS) or interferon γ(IFNγ) blocks macrophage proliferation. LPS treatment or M-CSF withdrawal arrests the cell cycle at early G1 and induces apoptosis. Treatment of macrophages with IFNγ stops the cell cycle later, at the G1/S boundary, induces p21(Waf1), and does not induce apoptosis. Moreover, pretreatment of macrophages with IFNγ protects from apoptosis induced by several stimuli. Inhibition of p21(Waf1) with antisense oligonucleotides or using KO mice shows that the induction of p21(Waf1) by IFNγ mediates this protection. Thus, IFNγ makes macrophages unresponsive to apoptotic stimuli by inducing p21(Waf1) and arresting the cell cycle at the G1/S boundary. Therefore, the cells of the innate immune system could only survive while they were functionally active.
AB - Incubation of bone marrow macrophages with lipopolysaccharide (LPS) or interferon γ(IFNγ) blocks macrophage proliferation. LPS treatment or M-CSF withdrawal arrests the cell cycle at early G1 and induces apoptosis. Treatment of macrophages with IFNγ stops the cell cycle later, at the G1/S boundary, induces p21(Waf1), and does not induce apoptosis. Moreover, pretreatment of macrophages with IFNγ protects from apoptosis induced by several stimuli. Inhibition of p21(Waf1) with antisense oligonucleotides or using KO mice shows that the induction of p21(Waf1) by IFNγ mediates this protection. Thus, IFNγ makes macrophages unresponsive to apoptotic stimuli by inducing p21(Waf1) and arresting the cell cycle at the G1/S boundary. Therefore, the cells of the innate immune system could only survive while they were functionally active.
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U2 - 10.1016/S1074-7613(00)80085-0
DO - 10.1016/S1074-7613(00)80085-0
M3 - Article
C2 - 10435583
AN - SCOPUS:0033166302
SN - 1074-7613
VL - 11
SP - 103
EP - 113
JO - Immunity
JF - Immunity
IS - 1
ER -