Over-expression of endothelin-1 in astrocytes, but not endothelial cells, ameliorates inflammatory pain response after formalin injection

Hung, Vivian Wing‐Yin; Chen, Samantha M. Y.; Tai, Wai Lydia; Chen, Ann Y.S.; Chung, Sookja K.; Cheung, Chun

doi:10.1016/j.lfs.2012.06.038

Cited by 17 publications

(13 citation statements)

References 20 publications

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“…On the other side, GET-1 mice but not TET-1 mice showed attenuated response to inflammatory pain induced by formalin injection compared to NTg mice. This suggests that chronic overexpression of astrocytic ET-1, but not endothelial ET-1, has a suppressor role in inflammatory pain (Hung et al, 2012). The findings of our study reveal that upon immunization with MOG 35-55 peptide, TET-1 and GET-1 mice developed more severe EAE compared to NTg mice, which is associated with increased infiltration of inflammatory cells including macrophages and demyelination in the spinal cord of the EAE mice.…”

Section: Discussionmentioning

confidence: 48%

“…Homozygous TET-1 and GET-1 mice were generated as described previously (Leung et al, 2004;Lo et al, 2005;Hung et al, 2012). In brief, heterozygous TET-1 and GET-1 mice were generated by microinjection of constructs containing mouse ET-1 cDNA containing SV40 polyA sequence in which transgene expression was driven by endothelial cell-specific receptor tyrosine kinase (tie-1) or astrocytespecific glial fibrillary acidic protein (GFAP) promotor, respectively.…”

Section: Et-1 Transgenic and Non-transgenic Micementioning

confidence: 99%

“…Heterozygous TET-1 or GET-1 mice were then backcrossed for 5 generations with wild-type C57BL/6N mice to obtain homozygous TET-1 or GET-1 mice. Genotyping was performed using Southern blot and PCR analysis as described previously (Leung et al, 2004;Lo et al, 2005;Hung et al, 2012). The total ET-1 mRNA level in the brain of TET-1 mice was about 2-fold of that of non-transgenic (NTg) mice, and plasma ET-1 level of TET-1 mice was about 1.4 fold of that of NTg mice (p b 0.05) (Leung et al, 2004;Hung et al, 2012).…”

Section: Et-1 Transgenic and Non-transgenic Micementioning

confidence: 99%

“…Genotyping was performed using Southern blot and PCR analysis as described previously (Leung et al, 2004;Lo et al, 2005;Hung et al, 2012). The total ET-1 mRNA level in the brain of TET-1 mice was about 2-fold of that of non-transgenic (NTg) mice, and plasma ET-1 level of TET-1 mice was about 1.4 fold of that of NTg mice (p b 0.05) (Leung et al, 2004;Hung et al, 2012). The total ET-1 mRNA level in the brain of GET-1 mice was about 18-fold of that of NTg mice, and plasma ET-1 level of heterozygous GET-1 mice was about 2-fold of that of NTg mice (Lo et al, 2005).…”

Section: Et-1 Transgenic and Non-transgenic Micementioning

confidence: 99%

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Endothelin-1 overexpression exacerbate experimental allergic encephalomyelitis

Guo¹,

Chung

Siu

et al. 2014

Journal of Neuroimmunology

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Section: Discussionmentioning

confidence: 48%

Section: Et-1 Transgenic and Non-transgenic Micementioning

confidence: 99%

Section: Et-1 Transgenic and Non-transgenic Micementioning

confidence: 99%

Section: Et-1 Transgenic and Non-transgenic Micementioning

confidence: 99%

See 2 more Smart Citations

Endothelin-1 overexpression exacerbate experimental allergic encephalomyelitis

Guo¹,

Chung

Siu

et al. 2014

Journal of Neuroimmunology

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“…At the spinal cord level, ET-1 concentration increases after peripheral tissue injury in rats submitted to chronic post-ischemia pain (Kim et al 2015). An anti-nociceptive effect of spinal cord ET-1 production has been reported in animal models of neuropathic and inflammatory pain (Hung et al 2012;Hung et al 2014), and on the other hand, spinal ET-1 induces mechanical hyperalgesia in a model of ischemia/reperfusion-induced oxidative stress (Kim et al 2015). Therefore, a pro-or antinociceptive role for ET-1 is not totally predictable.…”

Section: Introductionmentioning

confidence: 99%

Bosentan, a mixed endothelin receptor antagonist, inhibits superoxide anion-induced pain and inflammation in mice

Serafim

Navarro

Zarpelon

et al. 2015

Naunyn-Schmiedeberg's Arch Pharmacol

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Bosentan is a mixed endothelin receptor antagonist widely used to treat patients with pulmonary arterial hypertension, and the emerging literature suggests bosentan as a potent anti-inflammatory drug. Superoxide anion is produced in large amounts during inflammation, stimulates cytokine production, and thus contributes to inflammation and pain. However, it remains to be determined whether endothelin contributes to the inflammatory response triggered by the superoxide anion. The present study investigated the effects of bosentan in a mouse model of inflammation and pain induced by potassium superoxide, a superoxide anion donor. Male Swiss mice were treated with bosentan (10-100 mg/kg) by oral gavage, 1 h before potassium superoxide injection, and the inflammatory response was evaluated locally and at spinal cord (L4-L6) levels. Bosentan (100 mg/kg) inhibited superoxide anion-induced mechanical and thermal hyperalgesia, overt pain-like behavior (abdominal writhings, paw flinching, and licking), paw edema, myeloperoxidase activity (neutrophil marker) in the paw skin, and leukocyte recruitment in the peritoneal cavity. Bosentan also inhibited superoxide anion-induced interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) production, while it enhanced IL-10 production in the paw skin and spinal cord. Bosentan inhibited the reduction of antioxidant capacity (reduced glutathione, ferric reducing antioxidant power, and ABTS radical scavenging ability) induced by the superoxide anion. Finally, we demonstrated that intraplantar injection of potassium superoxide induces the mRNA expression of prepro-endothelin-1 in the paw skin and spinal cord. In conclusion, our results demonstrated that superoxide anion-induced inflammation, pain, cytokine production, and oxidative stress depend on endothelin; therefore, these responses are amenable to bosentan treatment.

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Proteome of brain glia: The molecular basis of diverse glial phenotypes

2013

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Several different types of nonneuronal glial cells with diverse phenotypes are present in the CNS, and all have distinct indispensible functions. Although glial cells primarily provide neurons with metabolic and structural support in the healthy brain, they may switch phenotype from a "resting" to a "reactive" state in response to pathological insults. Furthermore, this reactive gliosis is an invariant feature of the pathogeneses of CNS maladies. The glial proteome serves as a signature of glial phenotype, and not only executes physiological functions, but also acts as a molecular mediator of the reactive glial phenotype. The glial proteome is also involved in intra- and intercellular communications as exemplified by glia-glia and neuron-glia interactions. The utilization of authoritative proteomic tools and the bioinformatic analyses have helped to profile the brain glial proteome and explore the molecular mechanisms of diverse glial phenotypes. Furthermore, technologic innovations have equipped the field of "glioproteomics" with refined tools for studies of the expression, interaction, and function of glial proteins in the healthy and in the diseased CNS. Glioproteomics is expected to contribute to the elucidation of the molecular mechanisms of CNS pathophysiology and to the discovery of biomarkers and theragnostic targets in CNS disorders.

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Over-expression of endothelin-1 in astrocytes, but not endothelial cells, ameliorates inflammatory pain response after formalin injection

Abstract: The current results support a suppressor role for astrocyte-derived ET-1 in inflammatory pain and suggest that the study of GET-1 mice might provide mechanistic insights for improving the treatment of inflammatory pain.

Cited by 17 publications

References 20 publications

Endothelin-1 overexpression exacerbate experimental allergic encephalomyelitis

Endothelin-1 overexpression exacerbate experimental allergic encephalomyelitis

Bosentan, a mixed endothelin receptor antagonist, inhibits superoxide anion-induced pain and inflammation in mice

Proteome of brain glia: The molecular basis of diverse glial phenotypes

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