Lipopolysaccharide-mediated Reactive Oxygen Species and Signal Transduction in the Regulation of Interleukin-1 Gene Expression

Hsu, Hsien Yeh; Wen, Meng Hsuan

doi:10.1074/jbc.m111883200

Cited by 471 publications

(394 citation statements)

References 70 publications

Supporting

Mentioning

358

Contrasting

Unclassified

Order By: Relevance

“…It has also been reported that p38 and ERK pathways play an important role in IL-1b and TNF-a production, respectively (Hsu and Wen 2002;Shi et al 2002). Herein, our data demonstrate that all three types of MAPKs are activated in cisplatin-treated cells.…”

Section: Fig 10supporting

confidence: 76%

Cisplatin Cytotoxicity of Auditory Cells Requires Secretions of Proinflammatory Cytokines via Activation of ERK and NF-κB

Kim

Lee

et al. 2007

JARO

219

211

View full text Add to dashboard Cite

The ototoxicity of cisplatin, a widely used chemotherapeutic agent, involves a number of mechanisms, including perturbation of redox status, increase in lipid peroxidation, and formation of DNA adducts. In this study, we demonstrate that cisplatin increased the early immediate release and de novo synthesis of proinflammatory cytokines, including TNF-a, IL-1b, and IL-6, through the activation of ERK and NF-kB in HEI-OC1 cells, which are conditionally immortalized cochlear cells that express hair cell markers. Both neutralization of proinflammatory cytokines and pharmacologic inhibition of ERK significantly attenuated the death of HEI-OC1 auditory cells caused by cisplatin and proinflammatory cytokines. We also observed a significant increase in the protein and mRNA levels of proinflammatory cytokines in both serum and cochleae of cisplatin-injected rats, which was suppressed by intraperitoneal injection of etanercept, an inhibitor of TNF-a. Immunohistochemical studies revealed that TNF-a expression was mainly located in the spiral ligament, spiral limbus, and the organ of Corti in the cochleae of cisplatin-injected rats. NF-kB protein expression, which overlapped with terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling-positive signal, was very strong in specific regions of the cochleae, including the organ of Corti, spiral ligament, and stria vascularis. These results indicate that proinflammatory cytokines, especially TNF-a, play a central role in the pathophysiology of sensory hair cell damage caused by cisplatin.

show abstract

Section: Fig 10supporting

confidence: 76%

Cisplatin Cytotoxicity of Auditory Cells Requires Secretions of Proinflammatory Cytokines via Activation of ERK and NF-κB

Kim

Lee

et al. 2007

JARO

219

211

View full text Add to dashboard Cite

show abstract

“…For example, it has been reported that the p38 and ERK pathways play an important role in IL-1β and TNF-α production, respectively (Hsu and Wen 2002;Shi et al 2002). Therefore, we speculated that modulation of other signaling events involving MAPKs by flunarizine might affect the activation of NF-κB by cisplatin and consequently attenuate pro-inflammatory cytokine production and apoptotic cell death after cisplatin exposure.…”

Section: Discussionmentioning

confidence: 99%

Evidence that Cisplatin-induced Auditory Damage is Attenuated by Downregulation of Pro-inflammatory Cytokines Via Nrf2/HO-1

Kim

et al. 2008

JARO

111

View full text Add to dashboard Cite

Recently, we demonstrated that pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 played a critical role in cisplatin-induced cochlear injury and that flunarizine, known as a T-type Ca 2+ channel antagonist, induced a cytoprotective effect against cisplatin cytotoxicity in HEI-OC1 cells by the activation of NF-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) cascade through PI3K-Akt signaling but calciumindependent pathway. We report here that flunarizine markedly attenuates cisplatin-induced pro-inflammatory cytokine secretion and their messenger RNA transcription as well as cisplatin cytotoxicity through the activation of Nrf2/HO-1 and downregulation of NF-κB. In HEI-OC1 cells, overexpression of Nrf2/HO-1 by gene transfer or pharmacological approaches attenuated cisplatin-induced cytotoxicity and proinflammatory cytokine production. On the contrary, inhibition of Nrf2/HO-1 signaling by pharmacological inhibitors or specific small interfering RNAs significantly abolished the beneficial effects of flunarizine. Flunarizine also attenuated cisplatin-mediated MAPK activation and pharmacological inhibition of MAPKs, especially MEK1/ERK, blocked cisplatin-induced NF-κB activation in HEI-OC1 cells. Furthermore, WT-Nrf2 overexpression effectively blocked MAPK activation after cisplatin exposure. Finally, orally administrated Sibelium™, the trade name of flunarizine, suppressed the increase of pro-inflammatory cytokines by cisplatin in both serum and cochleas of mice, whereas it increased HO-1 expression in cochleas. These results indicate that flunarizine induces a protective effect against cisplatin ototoxicity through the downregulation of NF-κB by Nrf2/HO-1 activation and the resulting inhibition of pro-inflammatory cytokine production in vitro and in vivo.

show abstract

“…a protein) produced by targeted cells and passed on through the medium or the induction of a (secondary) bystander signal in the Mechanisms of bystander cH2AX foci induction S Burdak-Rothkamm et al bystander cells themselves. As some cytokines can be induced by increased ROS levels (Bellocq et al, 1999;Ayache et al, 2002;Hsu and Wen, 2002;Kosmidou et al, 2002;Hwang et al, 2004;Ryan et al, 2004), they are likely candidates for a secondary bystander signal. Furthermore, some of these cytokines (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…The involvement of soluble factors like reactive oxygen species (ROS) (Azzam et al, 2002;Shao et al, 2003aShao et al, , 2005, nitric oxide (NO) (Shao et al, 2003b(Shao et al, , 2005Sokolov et al, 2005) and cytokines released from irradiated cells as well as gap junction intercellular communication (Azzam et al, 2001;Shao et al, 2003a;Mitchell et al, 2004;Sokolov et al, 2005) have recently been reported. Most interestingly, several cytokines can be induced by ROS and NO/NOS (Ayache et al, 2002;Hsu and Wen, 2002;Kosmidou et al, 2002;Hwang et al, 2004;Ryan et al, 2004) providing a possible link between different factors potentially involved in bystander signalling. End points used for the study of bystander effects in vitro have included micronuclei formation (Azzam et al, 2002;Kashino et al, 2004;Shao et al, 2004), gene mutations and genomic instability (Zhou et al, 2000), gene expression changes (Azzam et al, 2002;Yang et al, 2005), transformation (Sawant et al, 2001), proliferation (Gerashchenko and Howell, 2003), cell survival, apoptosis (Belyakov et al, 2002;Lyng et al, 2002), cell cycle arrest (Azzam et al, 2000) and most recently the induction of gH2AX foci in bystander cells (Hu et al, 2005;Sokolov et al, 2005;Yang et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

ATR-dependent radiation-induced γH2AX foci in bystander primary human astrocytes and glioma cells

et al. 2006

View full text Add to dashboard Cite

Lipopolysaccharide-mediated Reactive Oxygen Species and Signal Transduction in the Regulation of Interleukin-1 Gene Expression

Abstract: Lipopolysaccharide (LPS) stimulates macrophages to release inflammatory cytokines, interleukin-1␤ (IL-1), and tumor necrosis factor (TNF). LPS-induced TNF

Cited by 471 publications

References 70 publications

Cisplatin Cytotoxicity of Auditory Cells Requires Secretions of Proinflammatory Cytokines via Activation of ERK and NF-κB

Cisplatin Cytotoxicity of Auditory Cells Requires Secretions of Proinflammatory Cytokines via Activation of ERK and NF-κB

Evidence that Cisplatin-induced Auditory Damage is Attenuated by Downregulation of Pro-inflammatory Cytokines Via Nrf2/HO-1

ATR-dependent radiation-induced γH2AX foci in bystander primary human astrocytes and glioma cells

Contact Info

Product

Resources

About