Gene interactions and pathways from curated databases and text-mining
J Cell Physiol 2010, PMID: 20432452

Interleukin-1beta induces ICAM-1 expression enhancing leukocyte adhesion in human rheumatoid arthritis synovial fibroblasts: involvement of ERK, JNK, AP-1, and NF-kappaB.

Yang, Chuen-Mao; Luo, Shue-Fen; Hsieh, Hsi-Lung; Chi, Pei-Ling; Lin, Chih-Chung; Wu, Chi-Chuan; Hsiao, Li-Der

Interleukin-1beta (IL-1beta) has been shown to induce the expression of adhesion molecules on various cell types and contributes to inflammatory responses. However, the molecular mechanisms by which IL-1beta induced intercellular adhesion molecule (ICAM)-1 expression remain unclear in human rheumatoid arthritis synovial fibroblasts (RASFs). Here, we demonstrated that IL-1beta induces ICAM-1 gene expression via the de novo protein synthesis through transcription and translation, which is attenuated by pretreatment with actinomycin D and cycloheximide, respectively. IL-1beta-induced ICAM-1 expression, extracellular signal-regulated kinase (ERK) and c-Jun-N-terminal kinase (JNK) phosphorylation, AP-1 activation, and nuclear factor-kappaB (NF-kappaB) p65 translocation were attenuated by the inhibitors of MEK1/2 (U0126), JNK (SP600125), AP-1 (tanshinone IIA), and NF-kappaB (helenalin) or transfection with respective short hairpin RNA plasmids. Moreover, IL-1beta-stimulated NF-kappaB p65 translocation was blocked by helenalin, but not by U0126 or SP600125, revealing that MAPKs and NF-kappaB pathways were independent on these responses. IL-1beta-stimulated AP-1 activation was blocked by U0126 or SP600125, revealing that ERK and JNK linked to AP-1 on these responses. IL-1beta-stimulated ICAM-1 gene expression was attenuated by pretreatment with U0126, SP600125, tanshinone IIA, or helenalin, revealed by ICAM-1 promoter assay and real-time RT-PCR analysis. Finally, up-regulation of ICAM-1 enhanced the adhesion of leukocytes to RASFs exposed to IL-1beta. These results suggest that in human RASFs, activation of ERK, JNK, AP-1, and NF-kappaB are essential for IL-1beta-induced ICAM-1 expression and leukocyte adhesion.

Diseases/Pathways annotated by Medline MESH: Arthritis, Rheumatoid
Document information provided by NCBI PubMed

Text Mining Data

ICAM-1 → Interleukin-1beta: " Interleukin-1beta induces ICAM-1 expression enhancing leukocyte adhesion in human rheumatoid arthritis synovial fibroblasts : involvement of ERK, JNK, AP-1, and NF-kappaB "

ICAM-1 → IL-1beta: " Here, we demonstrated that IL-1beta induces ICAM-1 gene expression via the de novo protein synthesis through transcription and translation, which is attenuated by pretreatment with actinomycin D and cycloheximide, respectively "

p65 → AP-1: " IL-1beta induced ICAM-1 expression, extracellular signal regulated kinase ( ERK ) and c-Jun-N-terminal kinase (JNK) phosphorylation, AP-1 activation, and nuclear factor-kappaB (NF-kappaB) p65 translocation were attenuated by the inhibitors of MEK1/2 ( U0126 ), JNK ( SP600125 ), AP-1 ( tanshinone IIA ), and NF-kappaB ( helenalin ) or transfection with respective short hairpin RNA plasmids "

p65 → IL-1beta: " IL-1beta induced ICAM-1 expression, extracellular signal regulated kinase ( ERK ) and c-Jun-N-terminal kinase (JNK) phosphorylation, AP-1 activation, and nuclear factor-kappaB (NF-kappaB) p65 translocation were attenuated by the inhibitors of MEK1/2 ( U0126 ), JNK ( SP600125 ), AP-1 ( tanshinone IIA ), and NF-kappaB ( helenalin ) or transfection with respective short hairpin RNA plasmids "

p65 → MEK1/2: " IL-1beta induced ICAM-1 expression, extracellular signal regulated kinase ( ERK ) and c-Jun-N-terminal kinase (JNK) phosphorylation, AP-1 activation, and nuclear factor-kappaB (NF-kappaB) p65 translocation were attenuated by the inhibitors of MEK1/2 ( U0126 ), JNK ( SP600125 ), AP-1 ( tanshinone IIA ), and NF-kappaB ( helenalin ) or transfection with respective short hairpin RNA plasmids "

p65 → NF-kappaB: " IL-1beta induced ICAM-1 expression, extracellular signal regulated kinase ( ERK ) and c-Jun-N-terminal kinase (JNK) phosphorylation, AP-1 activation, and nuclear factor-kappaB (NF-kappaB) p65 translocation were attenuated by the inhibitors of MEK1/2 ( U0126 ), JNK ( SP600125 ), AP-1 ( tanshinone IIA ), and NF-kappaB ( helenalin ) or transfection with respective short hairpin RNA plasmids "

AP-1 → IL-1beta: " IL-1beta induced ICAM-1 expression, extracellular signal regulated kinase ( ERK ) and c-Jun-N-terminal kinase (JNK) phosphorylation, AP-1 activation , and nuclear factor-kappaB (NF-kappaB) p65 translocation were attenuated by the inhibitors of MEK1/2 ( U0126 ), JNK ( SP600125 ), AP-1 ( tanshinone IIA ), and NF-kappaB ( helenalin ) or transfection with respective short hairpin RNA plasmids "

AP-1 → MEK1/2: " IL-1beta induced ICAM-1 expression, extracellular signal regulated kinase ( ERK ) and c-Jun-N-terminal kinase (JNK) phosphorylation, AP-1 activation, and nuclear factor-kappaB (NF-kappaB) p65 translocation were attenuated by the inhibitors of MEK1/2 ( U0126 ), JNK ( SP600125 ), AP-1 ( tanshinone IIA ), and NF-kappaB ( helenalin ) or transfection with respective short hairpin RNA plasmids "

AP-1 → NF-kappaB: " IL-1beta induced ICAM-1 expression, extracellular signal regulated kinase ( ERK ) and c-Jun-N-terminal kinase (JNK) phosphorylation, AP-1 activation, and nuclear factor-kappaB (NF-kappaB) p65 translocation were attenuated by the inhibitors of MEK1/2 ( U0126 ), JNK ( SP600125 ), AP-1 ( tanshinone IIA ), and NF-kappaB ( helenalin ) or transfection with respective short hairpin RNA plasmids "

ICAM-1 → AP-1: " IL-1beta induced ICAM-1 expression, extracellular signal regulated kinase ( ERK ) and c-Jun-N-terminal kinase (JNK) phosphorylation, AP-1 activation, and nuclear factor-kappaB (NF-kappaB) p65 translocation were attenuated by the inhibitors of MEK1/2 ( U0126 ), JNK ( SP600125 ), AP-1 ( tanshinone IIA ), and NF-kappaB ( helenalin ) or transfection with respective short hairpin RNA plasmids "

ICAM-1 → IL-1beta: " IL-1beta induced ICAM-1 expression, extracellular signal regulated kinase ( ERK ) and c-Jun-N-terminal kinase (JNK) phosphorylation, AP-1 activation, and nuclear factor-kappaB (NF-kappaB) p65 translocation were attenuated by the inhibitors of MEK1/2 ( U0126 ), JNK ( SP600125 ), AP-1 ( tanshinone IIA ), and NF-kappaB ( helenalin ) or transfection with respective short hairpin RNA plasmids "

ICAM-1 → MEK1/2: " IL-1beta induced ICAM-1 expression, extracellular signal regulated kinase ( ERK ) and c-Jun-N-terminal kinase (JNK) phosphorylation, AP-1 activation, and nuclear factor-kappaB (NF-kappaB) p65 translocation were attenuated by the inhibitors of MEK1/2 ( U0126 ), JNK ( SP600125 ), AP-1 ( tanshinone IIA ), and NF-kappaB ( helenalin ) or transfection with respective short hairpin RNA plasmids "

ICAM-1 → NF-kappaB: " IL-1beta induced ICAM-1 expression, extracellular signal regulated kinase ( ERK ) and c-Jun-N-terminal kinase (JNK) phosphorylation, AP-1 activation, and nuclear factor-kappaB (NF-kappaB) p65 translocation were attenuated by the inhibitors of MEK1/2 ( U0126 ), JNK ( SP600125 ), AP-1 ( tanshinone IIA ), and NF-kappaB ( helenalin ) or transfection with respective short hairpin RNA plasmids "

c-Jun-N-terminal kinase (JNK) → AP-1: " IL-1beta induced ICAM-1 expression, extracellular signal regulated kinase ( ERK ) and c-Jun-N-terminal kinase (JNK) phosphorylation, AP-1 activation, and nuclear factor-kappaB (NF-kappaB) p65 translocation were attenuated by the inhibitors of MEK1/2 ( U0126 ), JNK ( SP600125 ), AP-1 ( tanshinone IIA ), and NF-kappaB ( helenalin ) or transfection with respective short hairpin RNA plasmids "

nuclear factor-kappaB (NF-kappaB) → IL-1beta: " IL-1beta induced ICAM-1 expression, extracellular signal regulated kinase ( ERK ) and c-Jun-N-terminal kinase (JNK) phosphorylation, AP-1 activation, and nuclear factor-kappaB (NF-kappaB) p65 translocation were attenuated by the inhibitors of MEK1/2 ( U0126 ), JNK ( SP600125 ), AP-1 ( tanshinone IIA ), and NF-kappaB ( helenalin ) or transfection with respective short hairpin RNA plasmids "

nuclear factor-kappaB (NF-kappaB) → MEK1/2: " IL-1beta induced ICAM-1 expression, extracellular signal regulated kinase ( ERK ) and c-Jun-N-terminal kinase (JNK) phosphorylation, AP-1 activation, and nuclear factor-kappaB (NF-kappaB) p65 translocation were attenuated by the inhibitors of MEK1/2 ( U0126 ), JNK ( SP600125 ), AP-1 ( tanshinone IIA ), and NF-kappaB ( helenalin ) or transfection with respective short hairpin RNA plasmids "

p65 → IL-1beta: " Moreover, IL-1beta stimulated NF-kappaB p65 translocation was blocked by helenalin, but not by U0126 or SP600125, revealing that MAPKs and NF-kappaB pathways were independent on these responses "

p65 → IL-1beta: " Moreover, IL-1beta stimulated NF-kappaB p65 translocation was blocked by helenalin, but not by U0126 or SP600125, revealing that MAPKs and NF-kappaB pathways were independent on these responses "

NF-kappaB → IL-1beta: " Moreover, IL-1beta stimulated NF-kappaB p65 translocation was blocked by helenalin, but not by U0126 or SP600125, revealing that MAPKs and NF-kappaB pathways were independent on these responses "

NF-kappaB → IL-1beta: " Moreover, IL-1beta stimulated NF-kappaB p65 translocation was blocked by helenalin, but not by U0126 or SP600125, revealing that MAPKs and NF-kappaB pathways were independent on these responses "

AP-1 → IL-1beta: " IL-1beta stimulated AP-1 activation was blocked by U0126 or SP600125, revealing that ERK and JNK linked to AP-1 on these responses "

ICAM-1 → IL-1beta: " IL-1beta stimulated ICAM-1 gene expression was attenuated by pretreatment with U0126, SP600125, tanshinone IIA, or helenalin, revealed by ICAM-1 promoter assay and real-time RT-PCR analysis "

ICAM-1 → ERK: " These results suggest that in human RASFs, activation of ERK , JNK, AP-1, and NF-kappaB are essential for IL-1beta induced ICAM-1 expression and leukocyte adhesion "

ICAM-1 → AP-1: " These results suggest that in human RASFs, activation of ERK, JNK, AP-1 , and NF-kappaB are essential for IL-1beta induced ICAM-1 expression and leukocyte adhesion "

ICAM-1 → IL-1beta: " These results suggest that in human RASFs, activation of ERK, JNK, AP-1, and NF-kappaB are essential for IL-1beta induced ICAM-1 expression and leukocyte adhesion "

ICAM-1 → NF-kappaB: " These results suggest that in human RASFs, activation of ERK, JNK, AP-1, and NF-kappaB are essential for IL-1beta induced ICAM-1 expression and leukocyte adhesion "

Manually curated Databases

No curated data.