Inhibitor of apoptosis (IAP) proteins in regulation of inflammation and innate immunity

TY - JOUR

T1 - Inhibitor of apoptosis (IAP) proteins in regulation of inflammation and innate immunity

AU - Damgaard, Rune B

AU - Gyrd-Hansen, Mads

PY - 2011/3

Y1 - 2011/3

N2 - Inflammatory and innate immune signaling in response to recognition of pathogens is essential for immunity and host survival. However, deregulation may lead to detrimental pathologies including immunodeficiency, inflammatory diseases, and cancer. Inhibitor of apoptosis (IAP) proteins have emerged as important regulators of innate immune signaling downstream of pattern recognition receptors (PRRs) such as Toll-like receptor 4 (TLR4), the nucleotide-binding oligomerization domain 1 (NOD1) and NOD2 receptors, and the retinoic acid-inducible gene (RIG)-I receptor. Recent evidence suggests that cIAP1, cIAP2, and XIAP facilitate ubiquitin-dependent signaling activated by these PRRs and mediate activation of nuclear factor-kappa B (NF-kappaB) transcription factors as well as the MAP kinases p38 and JNK. Here, we review the current understanding of IAP-mediated PRR signaling and how IAP proteins might present as promising targets for anti-inflammatory therapies in PRR-dependent inflammatory diseases including Crohn's disease, Blau syndrome, and septic shock.

AB - Inflammatory and innate immune signaling in response to recognition of pathogens is essential for immunity and host survival. However, deregulation may lead to detrimental pathologies including immunodeficiency, inflammatory diseases, and cancer. Inhibitor of apoptosis (IAP) proteins have emerged as important regulators of innate immune signaling downstream of pattern recognition receptors (PRRs) such as Toll-like receptor 4 (TLR4), the nucleotide-binding oligomerization domain 1 (NOD1) and NOD2 receptors, and the retinoic acid-inducible gene (RIG)-I receptor. Recent evidence suggests that cIAP1, cIAP2, and XIAP facilitate ubiquitin-dependent signaling activated by these PRRs and mediate activation of nuclear factor-kappa B (NF-kappaB) transcription factors as well as the MAP kinases p38 and JNK. Here, we review the current understanding of IAP-mediated PRR signaling and how IAP proteins might present as promising targets for anti-inflammatory therapies in PRR-dependent inflammatory diseases including Crohn's disease, Blau syndrome, and septic shock.

KW - Animals

KW - Humans

KW - Immunity, Innate

KW - Inflammation

KW - Inhibitor of Apoptosis Proteins

KW - NF-kappa B

KW - Nod2 Signaling

KW - Signal Transduction

KW - Toll-Like Receptor 4

M3 - Review

C2 - 21447281

SN - 1539-6509

VL - 11

SP - 221

EP - 231

JO - Discovery medicine

JF - Discovery medicine

IS - 58

ER -