Interferon gamma induces the expression of p21waf-1 and arrests macrophage cell cycle, preventing induction of apoptosis.
Incubation of bone marrow macrophages with lipopolysaccharide (LPS) or interferon gamma (IFN gamma) blocks macrophage proliferation. LPS treatment or M-CSF withdrawal arrests the cell cycle at early G1 and induces apoptosis. Treatment of macrophages with IFN gamma stops the cell cycle later, at the G1/S boundary, induces p21Waf1, and does not induce apoptosis. Moreover, pretreatment of macrophages with IFN gamma protects from apoptosis induced by several stimuli. Inhibition of p21Waf1 with antisense oligonucleotides or using KO mice shows that the induction of p21Waf1 by IFN gamma mediates this protection. Thus, IFN gamma makes macrophages unresponsive to apoptotic stimuli by inducing p21Waf1 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.
Xaus
J
J
Departament de Fisiologia (Biologia del macròfag), and Fundació August Pi i Sunyer, Universitat de Barcelona, Spain.
Cardó
M
M
Valledor
A F
AF
Soler
C
C
Lloberas
J
J
Celada
A
A
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001854:Bone Marrow Cells / Q000166:cytology; D002453:Cell Cycle / Q000235:genetics / Q000276:immunology*; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000037:antagonists & inhibitors / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D005434:Flow Cytometry; D006131:Growth Inhibitors / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology* / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016376:Oligonucleotides, Antisense / Q000494:pharmacology
C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D006131:Growth Inhibitors; D008070:Lipopolysaccharides; D016376:Oligonucleotides, Antisense; D019938:Cyclin D1; D007334:Insulin-Like Growth Factor I; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma