Gene interactions and pathways from curated databases and text-mining
J Biol Chem 2005, PMID: 15591054

Interleukin-8 induces nuclear transcription factor-kappaB through a TRAF6-dependent pathway.

Manna, Sunil K; Ramesh, Govindarajan T

Considering the potential role of interleukin-8 (IL-8) in inflammation, angiogenesis, tumorigenesis, and metastasis, we investigated the molecular mechanism involved in IL-8-mediated signaling. In this report we provide evidence that like TNF, an inducer of NF-kappaB and also a NF-kappaB-dependent gene product, IL-8 induces NF-kappaB in a unique pathway. IL-8 induces NF-kappaB activation in a dose-dependent manner in different cell types as detected by a DNA-protein binding assay. IL-8 induces NF-kappaB-dependent reporter gene expression as well as ICAM-1, VCAM-1, and Cox-2 expression. IL-8 also induces IkappaBalpha phosphorylation followed by degradation and p65 translocation. IL-8 induces c-Jun N-terminal kinase (JNK) and mitogen-activated protein kinase (MAPK) in a dose- and time-dependent manner. IL-8-induced NF-kappaB activation is for the most part unaltered when cells are transfected with dominant-negative TRADD, FADD, or TRAF2, but is inhibited with dominant-negative TRAF6-, NIK-, IKK-, or IkappaBalpha-transfected cells. The data suggest that IL-8-induced NF-kappaB activation proceeds through a TRAF2-independent but TRAF6-dependent pathway, followed by recruitment of IRAK and activation of IKK. IL-8-induced NF-kappaB activation is not observed in a cell-permeable peptide that has TRAF6 binding motif-treated cells or IRAK-deficient cells. IL-8-induced NF-kappaB activation proceeds mostly through interaction with TRAF6 and partially through the Rho-GTPase pathways. This is the first report that IL-8 induces NF-kappaB in a distinct pathway, and activation of NF-kappaB and its dependent genes may be one of the pathways of IL-8-induced inflammation and angiogenesis.

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Text Mining Data

transcription factor-kappaB → Interleukin-8: " Interleukin-8 induces nuclear transcription factor-kappaB through a TRAF6 dependent pathway "

NF-kappaB → IL-8: " In this report we provide evidence that like TNF, an inducer of NF-kappaB and also a NF-kappaB dependent gene product, IL-8 induces NF-kappaB in a unique pathway "

IL-8 → NF-kappaB: " IL-8 induces NF-kappaB activation in a dose dependent manner in different cell types as detected by a DNA-protein binding assay "

VCAM-1 → IL-8: " IL-8 induces NF-kappaB dependent reporter gene expression as well as ICAM-1, VCAM-1 , and Cox-2 expression "

VCAM-1 → NF-kappaB: " IL-8 induces NF-kappaB dependent reporter gene expression as well as ICAM-1, VCAM-1 , and Cox-2 expression "

ICAM-1 → IL-8: " IL-8 induces NF-kappaB dependent reporter gene expression as well as ICAM-1 , VCAM-1, and Cox-2 expression "

ICAM-1 → NF-kappaB: " IL-8 induces NF-kappaB dependent reporter gene expression as well as ICAM-1 , VCAM-1, and Cox-2 expression "

IL-8 → NF-kappaB: " IL-8 induces NF-kappaB dependent reporter gene expression as well as ICAM-1, VCAM-1, and Cox-2 expression "

IL-8 → Cox-2: " IL-8 induces NF-kappaB dependent reporter gene expression as well as ICAM-1, VCAM-1, and Cox-2 expression "

Cox-2 → NF-kappaB: " IL-8 induces NF-kappaB dependent reporter gene expression as well as ICAM-1, VCAM-1, and Cox-2 expression "

IL-8 → IkappaBalpha: " IL-8 also induces IkappaBalpha phosphorylation followed by degradation and p65 translocation "

mitogen activated protein kinase → IL-8: " IL-8 induces c-Jun N-terminal kinase (JNK) and mitogen activated protein kinase ( MAPK ) in a dose- and time dependent manner "

c-Jun N-terminal kinase (JNK) → IL-8: " IL-8 induces c-Jun N-terminal kinase (JNK) and mitogen activated protein kinase ( MAPK ) in a dose- and time dependent manner "

NF-kappaB → IL-8: " IL-8 induced NF-kappaB activation is for the most part unaltered when cells are transfected with dominant negative TRADD, FADD, or TRAF2, but is inhibited with dominant negative TRAF6-, NIK-, IKK-, or IkappaBalpha transfected cells "

IRAK → IKK: " The data suggest that IL-8 induced NF-kappaB activation proceeds through a TRAF2 independent but TRAF6 dependent pathway, followed by recruitment of IRAK and activation of IKK "

NF-kappaB → IL-8: " The data suggest that IL-8 induced NF-kappaB activation proceeds through a TRAF2 independent but TRAF6 dependent pathway, followed by recruitment of IRAK and activation of IKK "

NF-kappaB → IL-8: " IL-8 induced NF-kappaB activation is not observed in a cell-permeable peptide that has TRAF6 binding motif treated cells or IRAK-deficient cells "

NF-kappaB → IL-8: " IL-8 induced NF-kappaB activation proceeds mostly through interaction with TRAF6 and partially through the Rho-GTPase pathways "

NF-kappaB → IL-8: " This is the first report that IL-8 induces NF-kappaB in a distinct pathway, and activation of NF-kappaB and its dependent genes may be one of the pathways of IL-8 induced inflammation and angiogenesis "

Manually curated Databases

No curated data.