Ethyl pyruvate decreases airway neutrophil infiltration partly through a high mobility group box 1-dependent mechanism in a chemical-induced murine asthma model

Tang, Haixiong; Zhao, Haijin; Song, Jingyu; Dong, Hangming; Yao, Le; Liang, Zhenyu; Lv, Yanhua; Zou, Fei; Cai, Shaoxi

doi:10.1016/j.intimp.2014.04.024

Cited by 34 publications

(31 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, higher level of HMGB1 has also been reported to be associated with impaired lung function and more severe disease in subjects with asthma (Hou et al, 2011;Watanabe et al, 2011). In a previous study, we have demonstrated a relationship between increased pulmonary expression of HMGB1 and allergic airway inflammation in TDI-induced murine asthma model (Tang et al, 2014). Yet how HMGB1 is regulated in the lung remains largely uncertain.…”

Section: Introductionmentioning

confidence: 89%

“…Lung tissues were stained with hematoxylin and eosin to assess pathological changes. Lung inflammation was semiquantified as described in our previous study (Tang et al, 2014).…”

Section: Lung Histopathologymentioning

confidence: 99%

“…Immunohistochemistry and western blot for HMGB1, caspase-1, IL-1b and NLRP3 were performed as previously described (Tang et al, 2014). Primary antibodies for HMGB1, caspase-1 and NLRP3 were obtained from Abcam (Hong Kong, China), and IL-1b from Santa Cruz (CA, USA).…”

Section: Immunohistochemistry and Western Blotmentioning

confidence: 99%

See 2 more Smart Citations

Phosphatidylinositol 3-kinases pathway mediates lung caspase-1 activation and high mobility group box 1 production in a toluene-diisocyanate induced murine asthma model

et al. 2015

Self Cite

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 89%

“…Lung tissues were stained with hematoxylin and eosin to assess pathological changes. Lung inflammation was semiquantified as described in our previous study (Tang et al, 2014).…”

Section: Lung Histopathologymentioning

confidence: 99%

See 1 more Smart Citation

Phosphatidylinositol 3-kinases pathway mediates lung caspase-1 activation and high mobility group box 1 production in a toluene-diisocyanate induced murine asthma model

et al. 2015

Self Cite

View full text Add to dashboard Cite

“…EP forms Michael-type adducts with thiols, activates Nrf2 in astrocytes, and inhibits NF-kB-dependent transcription in different cell types, including LPS-stimulated BV2 (microglial) cells and macrophage-like RAW 264.7 cells (10-13). Anti-inflammatory and neuroprotective effects of EP have been observed in animal models of sepsis, uveitis, and asthma (14)(15)(16). EP has been effective also against different neurologic insults, such as ischemia/reperfusion (17), intracerebral hemorrhageinduced brain injury (18), traumatic brain injury (19), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (20), LPS (21), and 3-nitropropionic acid (22).…”

mentioning

confidence: 99%

A Comparative Analysis of Multiple Sclerosis–Relevant Anti-Inflammatory Properties of Ethyl Pyruvate and Dimethyl Fumarate

Miljković

Blaževski

Petković

et al. 2015

The Journal of Immunology

View full text Add to dashboard Cite

Dimethyl fumarate (DMF), a new drug for multiple sclerosis (MS) treatment, acts against neuroinflammation via mechanisms that are triggered by adduct formation with thiol redox switches. Ethyl pyruvate (EP), an off-the-shelf agent, appears to be a redox analog of DMF, but its immunomodulatory properties have not been put into the context of MS therapy. In this article, we examined and compared the effects of EP and DMF on MS-relevant activity/functions of T cells, macrophages, microglia, and astrocytes. EP efficiently suppressed the release of MS signature cytokines, IFN-γ and IL-17, from human PBMCs. Furthermore, the production of these cytokines was notably decreased in encephalitogenic T cells after in vivo application of EP to rats. Production of two other proinflammatory cytokines, IL-6 and TNF, and NO was suppressed by EP in macrophages and microglia. Reactive oxygen species production in macrophages, microglia activation, and the development of Ag-presenting phenotype in microglia and macrophages were constrained by EP. The release of IL-6 was reduced in astrocytes. Finally, EP inhibited the activation of transcription factor NF-κB in microglia and astrocytes. Most of these effects were also found for DMF, implying that EP and DMF share common targets and mechanisms of action. Importantly, EP had in vivo impact on experimental autoimmune encephalomyelitis, an animal model of MS. Treatment with EP resulted in delay and shortening of the first relapse, and lower clinical scores, whereas the second attack was annihilated. Further studies on the possibility to use EP as an MS therapeutic are warranted.

show abstract

“…59 Treatment with EP would significantly decrease the levels of IL-4 and IL-13, therefore IgE synthesis may be down-regulated. Many studies of asthma, which is an allergic disease in the lower respiratory region, have proven that the blockage of HMGB1 activity with antibodies or agents such as EP will significantly decrease either total IgE or allergen-specific IgE levels, 13,22,60 indicating that EP administration may decrease total IgE levels by inhibiting HMGB1 expression. In addition, NF-kB is involved in the synthesis of IgE, and EP has been proven to be an effective agent for inhibiting NF-kB activity.…”

Section: Discussionmentioning

confidence: 99%

Ethyl pyruvate attenuates murine allergic rhinitis partly by decreasing high mobility group box 1 release

Chen

Wang

Gong

et al. 2015

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

High-mobility group box 1 (HMGB1) protein, a pro-inﬂammatory DNA-binding protein, meditates inflammatory responses through Toll-like receptor-4 signals and amplifies allergic inflammation by interacting with the receptor for advanced glycation end products. Previous studies have shown that HMGB1 is elevated in the nasal lavage fluids (NLF) of children suffering from allergic rhinitis (AR) and is associated with the severity of this disease. Furthermore, HMGB1 has been implicated in the pathogenesis of lower airway allergic diseases, such as asthma. Ethyl pyruvate (EP) has proven to be an effective anti-inflammatory agent for numerous airway diseases. Moreover, EP can inhibit the secretion of HMGB1. However, few studies have examined the effect of EP on AR. We hypothesized that HMGB1 plays an important role in the pathogenesis of AR and studied it using an AR mouse model. Forty BALB/c mice were divided into four groups: the control group, AR group, 50 mg/kg EP group, and 100 mg/kg EP group. The mice in the AR and EP administration groups received ovalbumin (OVA) sensitization and challenge, whereas those in the control group were given sterile saline instead of OVA. The mice in the EP administration group were given an intraperitoneal injection of EP 30 min before each OVA treatment. The number of nasal rubbings and sneezes of each mouse was counted after final treatment. Hematoxylin-eosin staining, AB-PAS staining, interleukin-4 and 13 in NLF, IgE, and the protein expression of HMGB1 were measured. Various features of the allergic inﬂammation after OVA exposure, including airway eosinophilia, Th-2 cytokine production, total IgE, and goblet cell hyperplasia were significantly inhibited by treatment with EP and the expression and release of HMGB1 were reduced after EP administration in a dose-dependent manner. These results indicate that HMGB1 is a potential therapeutic target of AR and that EP attenuates AR by decreasing HMGB1 expression.

show abstract

Ethyl pyruvate decreases airway neutrophil infiltration partly through a high mobility group box 1-dependent mechanism in a chemical-induced murine asthma model

Cited by 34 publications

References 55 publications

Phosphatidylinositol 3-kinases pathway mediates lung caspase-1 activation and high mobility group box 1 production in a toluene-diisocyanate induced murine asthma model

Phosphatidylinositol 3-kinases pathway mediates lung caspase-1 activation and high mobility group box 1 production in a toluene-diisocyanate induced murine asthma model

A Comparative Analysis of Multiple Sclerosis–Relevant Anti-Inflammatory Properties of Ethyl Pyruvate and Dimethyl Fumarate

Ethyl pyruvate attenuates murine allergic rhinitis partly by decreasing high mobility group box 1 release

Contact Info

Product

Resources

About