The mechanism by which MEK/ERK regulates JNK and p38 activity in polyamine depleted IEC-6 cells during apoptosis

Bavaria, Mitul; Jin, Shi; Ray, Ramesh M.; Johnson, Leonard R.

doi:10.1007/s10495-013-0944-1

Cited by 27 publications

(18 citation statements)

References 38 publications

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“…Previous studies investigated the crosstalk between ERK and JNK signaling pathways. The ERK activator MEK was reported to regulate JNK activity in rat intestine cell line (IEC-6) and in human astrocyte cell line (U-251) [ 47 , 48 ]. On the other hand, JNK activation was reported to inhibit ERK activation in COS-7 cells and in Bcr/Abl+ human leukemia cells [ 49 , 50 ].…”

Section: Resultsmentioning

confidence: 99%

ERK2 and JNK1 contribute to TNF-α-induced IL-8 expression in synovial fibroblasts

et al. 2017

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Tumor necrosis factor α (TNF-α) induces the expression and secretion of interleukin 8 (IL-8), which contributes to synovitis in rheumatoid arthritis (RA). To elucidate the mechanism of the onset of RA, we used synovial fibroblasts without autoimmune inflammatory diseases and investigated MAPK signaling pathways in TNF-α-induced IL-8 expression. Synovial fibroblasts isolated from healthy dogs were characterized by flow cytometry, which were positive for the fibroblast markers CD29, CD44, and CD90 but negative for the hematopoietic cell markers CD14, CD34, CD45, and HLA-DR. TNF-α stimulated the secretion and mRNA expression of IL-8 in a time- and dose-dependent manner. ERK and JNK inhibitors attenuated TNF-α-induced IL-8 expression and secretion. TNF-α induced the phosphorylation of ERK1/2 and JNK1/2. TNF-α-induced IL-8 expression was attenuated both in ERK2- and JNK1-knockdown cells. TNF-α-induced ERK1/2 or JNK1/2 was observed in ERK2- or JNK1-knockdown cells, respectively, showing that there is no crosstalk between ERK2 and JNK1 pathways. These observations indicate that the individual activation of ERK2 and JNK1 pathways contributes to TNF-α-induced IL-8 expression in synovial fibroblasts, which appears to be involved in the progress in RA.

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Section: Resultsmentioning

confidence: 99%

ERK2 and JNK1 contribute to TNF-α-induced IL-8 expression in synovial fibroblasts

et al. 2017

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“…MEK/ERK activity has been reported to regulate JNK activity in apoptotic signaling in IEC-6 cells derived from rat intestine50. In a human astrocyte cell line (U-251), MEK phosphorylated JNK51.…”

Section: Discussionmentioning

confidence: 99%

JNK activation is essential for activation of MEK/ERK signaling in IL-1β-induced COX-2 expression in synovial fibroblasts

Kitanaka

Nakano

Kitanaka

et al. 2017

Sci Rep

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The proinflammatory cytokine interleukin 1β (IL-1β) induces prostaglandin E2 (PGE2) production via upregulation of cyclooxygenase-2 (COX-2) expression in synovial fibroblasts. This effect of IL-1β is involved in osteoarthritis. We investigated MAPK signaling pathways in IL-1β-induced COX-2 expression in feline synovial fibroblasts. In the presence of MAPK inhibitors, IL-1β-induced COX-2 expression and PGE2 release were both attenuated. IL-1β induced the phosphorylation of p38, JNK, MEK, and ERK1/2. A JNK inhibitor prevented not only JNK phosphorylation but also MEK and ERK1/2 phosphorylation in IL-1β-stimulated cells, but MEK and ERK1/2 inhibitors had no effect on JNK phosphorylation. A p38 inhibitor prevented p38 phosphorylation, but had no effect on MEK, ERK1/2, and JNK phosphorylation. MEK, ERK1/2, and JNK inhibitors had no effect on p38 phosphorylation. We also observed that in IL-1β-treated cells, phosphorylated MEK, ERK1/2, and JNK were co-precipitated with anti-phospho-MEK, ERK1/2, and JNK antibodies. The silencing of JNK1 in siRNA-transfected fibroblasts prevented IL-1β to induce phosphorylation of MEK and ERK1/2 and COX-2 mRNA expression. These observations suggest that JNK1 phosphorylation is necessary for the activation of the MEK/ERK1/2 pathway and the subsequent COX-2 expression for PGE2 release, and p38 independently contributes to the IL-1β effect in synovial fibroblasts.

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“…[16] Bavaria et al reported in the apoptosis literature that MEK1/ERK1/2 negatively regulated JNK1/2 phosphorylation via induction of MAP kinase phosphatase-1 (MKP-1). [18] …”

Section: Discussionmentioning

confidence: 99%

Nonmineralized and Mineralized Collagen Scaffolds Induce Differential Osteogenic Signaling Pathways in Human Mesenchymal Stem Cells

Zhou

Ren

Bischoff

et al. 2017

Adv Healthcare Materials

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The instructive capabilities of extracellular matrix components in progenitor cell differentiation have recently generated significant interest in the development of bioinspired materials for regenerative applications. Previously, a correlation was described between the osteogenic capabilities of nanoparticulate mineralized collagen glycosaminoglycan scaffolds (MC-GAG) and an autogenous activation of small mothers against decapentaplegic ( Smad1/5) in the canonical bone morphogenetic protein receptor (BMPR) pathway with a diminished extracellular signal regulated kinase 1/2 (ERK1/2) activation when compared to nonmineralized collagen glycosaminoglycan scaffolds (Col-GAG). This work utilizes a canonical BMPR inhibitor (dorsomorphin homologue 1, DMH1) and an inhibitor of the mitogen activated protein kinase/ERK kinase (MEK)/(ERK) cascade (PD98059) to characterize the necessity of each pathway for osteogenesis. While DMH1 inhibits runt-related transcription factor 2 (Runx2) and bone sialoprotein II (BSPII) gene expression of primary human mesenchymal stem cells (hMSCs) on MC-GAG, PD98059 inhibits BSPII expression on Col-GAG independent of Runx2 expression. DMH1 inhibits mineralization on both Col-GAG and MC-GAG, however, PD98059 only inhibits mineralization on Col-GAG. DMH1 inhibits both Smad1/5 phosphorylation and Runx2 protein expression, whereas PD98059 inhibits ERK1/2 and c-Jun amino-terminal kinase 1/2 (JNK1/2) phosphorylation without affecting Runx2. Thus, activation of the canonical BMPR signaling is necessary for osteogenic differentiation and mineralization of hMSCs on Col-GAG or MC-GAG. The MEK/ERK cascade, intimately tied to JNK activation, is necessary for Runx2-independent osteogenesis on Col-GAG, while completely dispensable in osteogenesis on MC-GAG.

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The mechanism by which MEK/ERK regulates JNK and p38 activity in polyamine depleted IEC-6 cells during apoptosis

Cited by 27 publications

References 38 publications

ERK2 and JNK1 contribute to TNF-α-induced IL-8 expression in synovial fibroblasts

ERK2 and JNK1 contribute to TNF-α-induced IL-8 expression in synovial fibroblasts

JNK activation is essential for activation of MEK/ERK signaling in IL-1β-induced COX-2 expression in synovial fibroblasts

Nonmineralized and Mineralized Collagen Scaffolds Induce Differential Osteogenic Signaling Pathways in Human Mesenchymal Stem Cells

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