Bradykinin-stimulated p42/p44 MAPK activation associated with cell proliferation in corneal keratocytes

Cheng, Ching‐Yi; Huang, Song‐Chei; Hsiao, Li-Der; Sun, Chi-Chin; Jou, Mei‐Jie; Yang, Che‐Hua

doi:10.1016/j.cellsig.2003.09.005

Cited by 11 publications

(11 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…BK has been reported to act as an important mediator through activation of p42/p44 MAPK cascades in different cell types (Schwaninger et al, 1999;Xie et al, 2000;Liebmann, 2001;Cheng et al, 2004). Abnormal p42/p44 MAPK regulation might be implicated in several models of CNS injury and inflammation (Lee et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

BK‐induced cytosolic phospholipase A₂ expression via sequential PKC‐δ, p42/p44 MAPK, and NF‐κB activation in rat brain astrocytes

Hsieh

Hwang

et al. 2005

Journal Cellular Physiology

View full text Add to dashboard Cite

Bradykinin (BK), an inflammatory mediator, has been shown to induce cytosolic phospholipase A2 (cPLA2) expression implicating in inflammatory responses in various cell types. However, the detailed mechanisms underlying BK-induced cPLA2 expression in astrocytes remain unclear. RT-PCR and Western blotting analysis showed that BK induced the expression of cPLA2 mRNA and protein, which was inhibited by Hoe140, suggesting the involvement of B2 BK receptors, confirmed by immunofluorescence staining using anti-B2 BK receptor antibody. BK-induced cPLA2 expression and phosphorylation of p42/p44 MAPK was attenuated by PD98059, indicating the involvement of MEK1/2-p42/p44 MAPK in these responses. BK-induced cPLA2 expression might be due to the translocation of NF-kappaB into nucleus which was inhibited by Hoe140, helenalin, and PD98059, implying the involvement of NF-kappaB. Moreover, BK-induced cPLA2 expression was attenuated by rottlerin, suggesting that PKC-delta might be involved in these responses. This hypothesis was supported by the transfection with a dominant negative plasmid of PKC-delta significantly attenuated BK-induced response. In addition, BK-stimulated translocation of PKC-delta from cytosol to membrane fraction was inhibited by rottlerin but not by PD98059, indicating that PKC-delta might be an upstream component of p42/p44 MAPK. Accordingly, BK-induced phosphorylation of p42/p44 MAPK was attenuated by rottlerin but not by helenalin. These results suggest that in RBA-1 cells, BK-induced cPLA2 expression was sequentially mediated through activation of PKC-delta, p42/p44 MAPK, and NF-kappaB. Understanding the regulation of cPLA2 expression induced by BK in astrocytes might provide a new therapeutic strategy of brain injury and inflammatory diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

BK‐induced cytosolic phospholipase A₂ expression via sequential PKC‐δ, p42/p44 MAPK, and NF‐κB activation in rat brain astrocytes

Hsieh

Hwang

et al. 2005

Journal Cellular Physiology

View full text Add to dashboard Cite

show abstract

“…Several lines of evidence have shown that ERK1/2 are phosphorylated and translocated into nucleus by many GPCR agonists including BK (Cheng et al, 2004). To determine whether phosphor-ERK1/2 was translocated from cytoplasm into nucleus stimulated by BK in RBA-1 cells, nuclear fraction was prepared and analyzed by Western blotting assay.…”

Section: Bk Stimulates Translocation Of Phosphorylatedmentioning

confidence: 99%

Bradykinin induces matrix metalloproteinase‐9 expression and cell migration through a PKC‐δ‐dependent ERK/Elk‐1 pathway in astrocytes

Hsieh¹,

Wu²,

Yang³

2008

Glia

140

View full text Add to dashboard Cite

Many reports have shown that matrix metalloproteinase (MMP)-9 plays an important role in brain inflammation and diseases. In our previous study, bradykinin (BK) has been shown to induce proMMP-9 expression via MAPKs and NF-kappaB in rat brain astrocytes (RBA-1). However, the molecular mechanisms and physiological roles underlying BK-induced MMP-9 expression in RBA-1 remain unclear. Here we reported that BK induced proMMP-9 expression and promoted RBA-1 cell migration, via a B(2) BK receptor-activated protein kinase C-delta (PKC-delta)-dependent signaling pathway. Activation of PKC-delta led to phosphorylation and translocation of extracellular signal-regulated kinase 1/2 (ERK1/2) and then activated a transcription factor Elk-1. Phospho-Elk-1 bound to MMP-9 promoter and thereby induced transcription of MMP-9. The rat MMP-9 promoter containing an Elk-1 cis-binding site (Ets domain), that located at nucleotides -511 to -506 was identified as a crucial domain linking to BK action. Moreover, BK induced recruitment of p300 (as a transcriptional co-activator) to the MMP-9 promoter, leading to the acetylation of histone H4 in chromatin and facilitating MMP-9 gene transcription. Taken together, these results suggested that in RBA-1 cells, activation of ERK1/2 by a PKC-delta-dependent event mediated through Elk-1 pathway is essential for MMP-9 gene up-regulation and cell migration induced by BK.

show abstract

“…As far as we know, inappropriate up-regulation of COX-2 has been frequently observed in various premalignant and malignant tissues [Mohan and Epstein, 2003], and accumulating evidences have confirmed COX-2 as a major therapeutic target in the treatment of inflammatory disorders [Korotkova et al, 2005]. At the same time, the COX-2 expression is regulated by MAPKs in various cell types [Bradbury et al, 2004;Cheng et al, 2004], and NF-kB also plays a key role in the regulation of COX-2 expression in the different disease status [Ghosh and Karin, 2002]. So far, the role and the regulation of COX-2 expression have received considerable attentions.…”

mentioning

confidence: 99%

Anti‐inflammatory function of Withangulatin A by targeted inhibiting COX‐2 expression via MAPK and NF‐κB pathways

Sun

Liu

Cui

et al. 2009

J of Cellular Biochemistry

View full text Add to dashboard Cite

Withangulatin A (WA), an active component isolated from Physalis angulata L., has been reported to possess anti-tumor and trypanocidal activities in model systems via multiple biochemical mechanisms. The aim of this study is to investigate its anti-inflammatory potential and the possible underlying mechanisms. In the current study, WA significantly suppressed mice T lymphocytes proliferation stimulated with LPS in a dose- and time-dependent manner and inhibited pro-inflammation cytokines (IL-2, IFN-gamma, and IL-6) dramatically. Moreover, WA targeted inhibited COX-2 expression mediated by MAPKs and NF-kappaB nuclear translocation pathways in mice T lymphocytes, and this result was further confirmed by the COX-1/2 luciferase reporter assay. Intriguingly, administration of WA inhibited the extent of mice ear swelling and decreased pro-inflammatory cytokines production in mice blood serum. Based on these evidences, WA influences the mice T lymphocytes function through targeted inhibiting COX-2 expression via MAPKs and NF-kappaB nuclear translocation signaling pathways, and this would make WA a strong candidate for further study as an anti-inflammatory agent.

show abstract

Bradykinin-stimulated p42/p44 MAPK activation associated with cell proliferation in corneal keratocytes

Cited by 11 publications

References 29 publications

BK‐induced cytosolic phospholipase A₂ expression via sequential PKC‐δ, p42/p44 MAPK, and NF‐κB activation in rat brain astrocytes

BK‐induced cytosolic phospholipase A₂ expression via sequential PKC‐δ, p42/p44 MAPK, and NF‐κB activation in rat brain astrocytes

Bradykinin induces matrix metalloproteinase‐9 expression and cell migration through a PKC‐δ‐dependent ERK/Elk‐1 pathway in astrocytes

Anti‐inflammatory function of Withangulatin A by targeted inhibiting COX‐2 expression via MAPK and NF‐κB pathways

Contact Info

Product

Resources

About

Bradykinin-stimulated p42/p44 MAPK activation associated with cell proliferation in corneal keratocytes

Cited by 11 publications

References 29 publications

BK‐induced cytosolic phospholipase A2 expression via sequential PKC‐δ, p42/p44 MAPK, and NF‐κB activation in rat brain astrocytes

BK‐induced cytosolic phospholipase A2 expression via sequential PKC‐δ, p42/p44 MAPK, and NF‐κB activation in rat brain astrocytes

Bradykinin induces matrix metalloproteinase‐9 expression and cell migration through a PKC‐δ‐dependent ERK/Elk‐1 pathway in astrocytes

Anti‐inflammatory function of Withangulatin A by targeted inhibiting COX‐2 expression via MAPK and NF‐κB pathways

Contact Info

Product

Resources

About

BK‐induced cytosolic phospholipase A₂ expression via sequential PKC‐δ, p42/p44 MAPK, and NF‐κB activation in rat brain astrocytes

BK‐induced cytosolic phospholipase A₂ expression via sequential PKC‐δ, p42/p44 MAPK, and NF‐κB activation in rat brain astrocytes