Signaling pathways and genes that inhibit pathogen-induced macrophage apoptosis - CREB and NF-κB as key regulators

TY - JOUR

T1 - Signaling pathways and genes that inhibit pathogen-induced macrophage apoptosis - CREB and NF-κB as key regulators

AU - Park, Jin Mo

AU - Greten, Florian R.

AU - Wong, Athena

AU - Westrick, Randal J.

AU - Arthur, J. Simon C.

AU - Otsu, Kinya

AU - Hoffmann, Alexander

AU - Montminy, Marc

AU - Karin, Michael

PY - 2005/9

Y1 - 2005/9

N2 - Certain microbes evade host innate immunity by killing activated macrophages with the help of virulence factors that target prosurvival pathways. For instance, infection of macrophages with the TLR4-activating bacterium Bacillus anthracis triggers an apoptotic response due to inhibition of p38 MAP kinase activation by the bacterial-produced lethal toxin. Other pathogens induce macrophage apoptosis by preventing activation of NF-κB, which depends on IκB kinase β (IKKβ). To better understand how p38 and NF-κB maintain macrophage survival, we searched for target genes whose products prevent TLR4-induced apoptosis and a p38-dependent transcription factor required for their induction. Here we describe key roles for transcription factor CREB, a target for p38 signaling, and the plasminogen activator 2 (PAI-2) gene, a target for CREB, in maintenance of macrophage survival.

AB - Certain microbes evade host innate immunity by killing activated macrophages with the help of virulence factors that target prosurvival pathways. For instance, infection of macrophages with the TLR4-activating bacterium Bacillus anthracis triggers an apoptotic response due to inhibition of p38 MAP kinase activation by the bacterial-produced lethal toxin. Other pathogens induce macrophage apoptosis by preventing activation of NF-κB, which depends on IκB kinase β (IKKβ). To better understand how p38 and NF-κB maintain macrophage survival, we searched for target genes whose products prevent TLR4-induced apoptosis and a p38-dependent transcription factor required for their induction. Here we describe key roles for transcription factor CREB, a target for p38 signaling, and the plasminogen activator 2 (PAI-2) gene, a target for CREB, in maintenance of macrophage survival.

UR - https://www.scopus.com/pages/publications/24944554790

U2 - 10.1016/j.immuni.2005.08.010

DO - 10.1016/j.immuni.2005.08.010

M3 - Article

C2 - 16169504

AN - SCOPUS:24944554790

SN - 1074-7613

VL - 23

SP - 319

EP - 329

JO - Immunity

JF - Immunity

IS - 3

ER -