Critical role for apoptosis signal-regulating kinase 1 in the development of inflammatory K/BxN serum-induced arthritis

Mnich, Stephen J.; Blanner, Patrick M.; Hu, Lufei; Shaffer, Alexander F.; Happa, Fernando A.; O’Neil, Shawn P.; Ukairo, Okechukwu; Weiss, Dave; Welsh, Eric A.; Storer, Chad; Mbalaviele, Gabriel; Ichijo, Hidenori; Monahan, Joseph B.; Hardy, Medora M.; Eda, Hiroyuki

doi:10.1016/j.intimp.2010.06.023

Cited by 34 publications

(21 citation statements)

References 39 publications

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“…Apoptosis signal regulating kinase 1 (ASK1) is an important member of MAP3K family that activates both the JNK and p38 MAPK pathways in response to TNF-α stimulation (Nishitoh et al , 1998). ASK1 is activated by various types of stress, including oxidative stress, endoplasmic reticulum (ER) stress, calcium overload, and inflammatory cytokines such as TNF-α (Mnich et al , 2010; Philippe et al , 2013). However, the role of ASK1 in TNF-α signaling pathway to regulate IL-6 and IL-8 production, or the expression adhesion molecules in RA-FLS is still unknown.…”

Section: Introductionmentioning

confidence: 99%

Thymoquinone inhibits TNF-α-induced inflammation and cell adhesion in rheumatoid arthritis synovial fibroblasts by ASK1 regulation

Umar

Hedaya

Singh

et al. 2015

Toxicology and Applied Pharmacology

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Tumor necrosis factor-α (TNF-α) is a pro-inflammatory cytokine produced by monocytes/macrophage that plays a pathological role in rheumatoid arthritis (RA). In this study, we investigate the effect of thymoquinone (TQ), a phytochemical found in Nigella sativa, in regulating TNF-α-induced RA synovial fibroblast (RA-FLS) activation. Treatment with TQ (1–5 μM) had no marked effect on the viability of human RA-FLS. Pre-treatment of TQ inhibited TNF-α-induced interleukin-6 (IL-6) and IL-8 production and ICAM-1, VCAM-1, and cadherin-11 (Cad-11) expression in RA-FLS (p<0.01). Evaluation of the signaling events showed that TQ inhibited TNF-α-induced phospho-p38 and phospho-JNK expression, but had no inhibitory effect on NF-κB pathway, in RA-FLS (p<0.05; n=4). Interestingly, we observed that selective down-regulation of TNF-α-induced phospho-p38 and phospho-JNK activation by TQ is elicited through inhibition of apoptosis-regulated signaling kinase 1 (ASK1). Furthermore, TNF-α selectively induced phosphorylation of ASK1 at Thr845 residue in RA-FLS, which was inhibited by TQ pretreatment in a dose dependent manner (p<0.01). Pre-treatment of RA-FLS with ASK1 inhibitor (TC ASK10), blocked TNF-α induced expression of ICAM-1, VCAM-1, and Cad-11. Our results suggest that TNF-α-induced ASK1-p38/JNK pathway is an important mediator of cytokine synthesis and enhanced expression of adhesion molecule in RA-FLS and TQ, by selectively inhibiting this pathway, may have a potential therapeutic value in regulating tissue destruction observed in RA.

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Section: Introductionmentioning

confidence: 99%

Thymoquinone inhibits TNF-α-induced inflammation and cell adhesion in rheumatoid arthritis synovial fibroblasts by ASK1 regulation

Umar

Hedaya

Singh

et al. 2015

Toxicology and Applied Pharmacology

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“…Recently, Mnich et al 16 also showed that ASK1 is critical for the development of RA and is involved in the TNF-α-induced production of inflammatory mediators in the joint. We therefore decided to evaluate the role of miR-20a on ASK1 expression in RA FLS.…”

Section: Introductionmentioning

confidence: 99%

MiR-20a regulates ASK1 expression and TLR4-dependent cytokine release in rheumatoid fibroblast-like synoviocytes

et al. 2012

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“…The activation of ASK1 in both neural and glial cells plays a key role in neural cell death associated with the pathogenesis of various neurodegenerative diseases [39]. Previous report has been demonstrated that ASK1 knockout mice show markedly attenuation of edema, cartilage damage, and general inflammatory responses in model of rheumatoid arthritis [40]. ASK1 deficiency also found to attenuate CNS inflammation, demyelination, and glial activation in experimental encephalomyelitis [41].…”

Section: Discussionmentioning

confidence: 98%

Cobalt Protoporphyrin Upregulates Cyclooxygenase-2 Expression Through a Heme Oxygenase-Independent Mechanism

Lin¹,

Tsai

Lin

et al. 2015

Mol Neurobiol

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Cobalt protoporphyrin (CoPP) is a potent HO-1 inducer and generally known to be an antioxidant in various cell types. Little is known about the CoPP-induced cyclooxygenase-2 (COX-2) expression and its downstream signaling in microglial cells. In current study, CoPP caused concentration- and time-dependent increases in COX-2 expression in microglial cells. Furthermore, activation of apoptosis signal-regulating kinase (ASK) 1/MAP kinase involved in CoPP-induced COX-2 expression in microglia. CoPP also induced P2X7 receptor activation, and treatment of P2X7 inhibitors effectively reduced CoPP-induced COX-2 expression. Protein inhibitor of activated STAT (PIAS) 1 is reported to be involved in modulating anti-inflammatory response through negative regulation of transcription factors. Interestingly, treatment with CoPP markedly induced PIAS1 degradation which is regulated by PI3K, Akt, and glycogen synthase kinase 3α/β (GSK3α/β) signaling pathways. These results suggest that CoPP induces COX-2 expression through activating P2X7 receptors and ASK1/MAP kinases as well as PIAS1 degradation signaling pathways. Our study provides a new insight into the regulatory effect of CoPP on neuroinflammation in microglial cells.

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Critical role for apoptosis signal-regulating kinase 1 in the development of inflammatory K/BxN serum-induced arthritis

Cited by 34 publications

References 39 publications

Thymoquinone inhibits TNF-α-induced inflammation and cell adhesion in rheumatoid arthritis synovial fibroblasts by ASK1 regulation

Thymoquinone inhibits TNF-α-induced inflammation and cell adhesion in rheumatoid arthritis synovial fibroblasts by ASK1 regulation

MiR-20a regulates ASK1 expression and TLR4-dependent cytokine release in rheumatoid fibroblast-like synoviocytes

Cobalt Protoporphyrin Upregulates Cyclooxygenase-2 Expression Through a Heme Oxygenase-Independent Mechanism

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