Interferon-gamma enhances the apoptosis of macrophages under trophic stress through activation of p53 and the JAK1 pathway.
Apoptosis has been implicated as an important mediator of immunosuppression associated with a depleted nutritional state. Since a number of cytokines are likely to influence the rate of apoptosis, we determined the effect of interferon-gamma (IFN-gamma) on apoptosis of macrophages in serum/amino acid deprived cell culture conditions. IFN-gamma further increased the rate of apoptosis compared to trophically stressed macrophages. In addition, we showed that enhancement of apoptosis by IFN-gamma is caused by a decrease in mitochondrial membrane potential due to upregulation of p53 and Bax and down-regulation of Bcl-xL. Moreover, we found that IFN-gamma increases caspase-3 activity that had been induced by serum/amino acid depletion, and that JAK1 signaling is involved in capase-3 activation and in the enhancement of apoptosis by IFN-gamma.
Cho
Seong-Jun
SJ
Division of Immunopharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Korea.
Pyo
Suhkneung
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001202:Ascitic Fluid / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D015536:Down-Regulation; D005122:Exudates and Transudates / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D053613:Janus Kinase 1 / Q000096:biosynthesis*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D013312:Stress, Physiological; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis* / Q000378:metabolism; D051020:bcl-X Protein / Q000096:biosynthesis*
D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D007371:Interferon-gamma; D053613:Janus Kinase 1; D053148:Caspase 3