Gene interactions and pathways from curated databases and text-mining
Biochim Biophys Acta 2008, PMID: 18486623

Post-transcriptional regulation of TNF-induced expression of ICAM-1 and IL-8 in human lung microvascular endothelial cells: an obligatory role for the p38 MAPK-MK2 pathway dissociated with HSP27.

Su, Xin; Ao, Lihua; Zou, Ning; Song, Yong; Yang, Xiaoping; Cai, Guang-Yun; Fullerton, David A; Meng, Xianzhong

The tumor necrosis factor-alpha (TNF)-induced inflammatory response in human lung microvascular endothelial cells (MVECs) is an early event in acute lung injury. Studies have shown that p38 mitogen-activated protein kinase (MAPK), MAPK-activated protein kinase 2 (MK2) and heat shock protein 27 (HSP27) are involved in the expression of pro-inflammatory mediators in other cell types. However, their role in the TNF-induced inflammatory response in lung MVECs has not been determined. We evaluated the role of p38 MAPK, MK2 and HSP27 in regulating the TNF-induced expression of ICAM-1 and IL-8 in human lung MVECs. Inhibition of p38 MAPK reduced ICAM-1 and IL-8 expression without influencing NF-kappaB activation or ICAM-1 and IL-8 mRNA levels. TNF stimulation induced p38 MAPK-dependent phosphorylation of MK2 and HSP27. MK2 silencing reduced ICAM-1 and IL-8 expression without influencing NF-kappaB activation or ICAM-1 and IL-8 mRNA levels. HSP27 silencing reduced cellular HSP27 levels and HSP27 phosphorylation following TNF stimulation but had no effect on ICAM-1 and IL-8 expression. Our study demonstrates for the first time that MK2 mediates post-transcriptional regulation by p38 MAPK of the TNF-induced expression of ICAM-1 and IL-8 in human lung MVECs, and that this regulation by the p38 MAPK/MK2 pathway is dissociated from HSP27 phosphorylation.

Diseases/Pathways annotated by Medline MESH: MAP Kinase Signaling System
Document information provided by NCBI PubMed

Text Mining Data

ICAM-1 → TNF: " Post-transcriptional regulation of TNF induced expression of ICAM-1 and IL-8 in human lung microvascular endothelial cells : an obligatory role for the p38 MAPK-MK2 pathway dissociated with HSP27 "

IL-8 → TNF: " Post-transcriptional regulation of TNF induced expression of ICAM-1 and IL-8 in human lung microvascular endothelial cells : an obligatory role for the p38 MAPK-MK2 pathway dissociated with HSP27 "

ICAM-1 ⊣ MAPK: " We evaluated the role of p38 MAPK , MK2 and HSP27 in regulating the TNF induced expression of ICAM-1 and IL-8 in human lung MVECs "

ICAM-1 ⊣ HSP27: " We evaluated the role of p38 MAPK, MK2 and HSP27 in regulating the TNF induced expression of ICAM-1 and IL-8 in human lung MVECs "

ICAM-1 ⊣ MK2: " We evaluated the role of p38 MAPK, MK2 and HSP27 in regulating the TNF induced expression of ICAM-1 and IL-8 in human lung MVECs "

IL-8 ⊣ MAPK: " We evaluated the role of p38 MAPK , MK2 and HSP27 in regulating the TNF induced expression of ICAM-1 and IL-8 in human lung MVECs "

IL-8 ⊣ HSP27: " We evaluated the role of p38 MAPK, MK2 and HSP27 in regulating the TNF induced expression of ICAM-1 and IL-8 in human lung MVECs "

IL-8 ⊣ MK2: " We evaluated the role of p38 MAPK, MK2 and HSP27 in regulating the TNF induced expression of ICAM-1 and IL-8 in human lung MVECs "

ICAM-1 → TNF: " We evaluated the role of p38 MAPK, MK2 and HSP27 in regulating the TNF induced expression of ICAM-1 and IL-8 in human lung MVECs "

IL-8 → TNF: " We evaluated the role of p38 MAPK, MK2 and HSP27 in regulating the TNF induced expression of ICAM-1 and IL-8 in human lung MVECs "

ICAM-1 → MAPK: " Inhibition of p38 MAPK reduced ICAM-1 and IL-8 expression without influencing NF-kappaB activation or ICAM-1 and IL-8 mRNA levels "

IL-8 → MAPK: " Inhibition of p38 MAPK reduced ICAM-1 and IL-8 expression without influencing NF-kappaB activation or ICAM-1 and IL-8 mRNA levels "

TNF → p38: " TNF stimulation induced p38 MAPK dependent phosphorylation of MK2 and HSP27 "

TNF → HSP27: " TNF stimulation induced p38 MAPK dependent phosphorylation of MK2 and HSP27 "

TNF → MK2: " TNF stimulation induced p38 MAPK dependent phosphorylation of MK2 and HSP27 "

p38 → MAPK: " TNF stimulation induced p38 MAPK dependent phosphorylation of MK2 and HSP27 "

HSP27 → MAPK: " TNF stimulation induced p38 MAPK dependent phosphorylation of MK2 and HSP27 "

MK2 → MAPK: " TNF stimulation induced p38 MAPK dependent phosphorylation of MK2 and HSP27 "

ICAM-1 → TNF: " Our study demonstrates for the first time that MK2 mediates post-transcriptional regulation by p38 MAPK of the TNF induced expression of ICAM-1 and IL-8 in human lung MVECs, and that this regulation by the p38 MAPK/MK2 pathway is dissociated from HSP27 phosphorylation "

IL-8 → TNF: " Our study demonstrates for the first time that MK2 mediates post-transcriptional regulation by p38 MAPK of the TNF induced expression of ICAM-1 and IL-8 in human lung MVECs, and that this regulation by the p38 MAPK/MK2 pathway is dissociated from HSP27 phosphorylation "

ICAM-1 — MAPK: " Our study demonstrates for the first time that MK2 mediates post-transcriptional regulation by p38 MAPK of the TNF induced expression of ICAM-1 and IL-8 in human lung MVECs, and that this regulation by the p38 MAPK/MK2 pathway is dissociated from HSP27 phosphorylation "

IL-8 — MAPK: " Our study demonstrates for the first time that MK2 mediates post-transcriptional regulation by p38 MAPK of the TNF induced expression of ICAM-1 and IL-8 in human lung MVECs, and that this regulation by the p38 MAPK/MK2 pathway is dissociated from HSP27 phosphorylation "

Manually curated Databases

No curated data.