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

Liang, Jianying; Zhao, Haijin; Yao, Le; Tang, Haixiong; Dong, Hangming; Wu, Yue; Liu, Laiyu; Zou, Fei; Cai, Shaoxi

doi:10.1016/j.toxlet.2015.04.011

Cited by 36 publications

(26 citation statements)

References 49 publications

(61 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In TDI-induced murine asthma model, caspase-1 was activated after TDI exposure; after LY294002 adminstration was found abnormal distribution of cleaved caspase-1 but not procaspase-1, so the role of this specific inhibitor was established in the cleavage process of caspase-1 rather than increasing its protein expression. Also they detected higher level of IL-1b after TDI exposure, and showed that LY294002 administration reduced this TDI induced IL-1b expression in the cytoplasm [28]. …”

Section: Resultsmentioning

confidence: 99%

Association between HMGB1 and asthma: a literature review

et al. 2017

View full text Add to dashboard Cite

BackgroundRecently, some studies demonstrated that HMGB1, as proinflammatory mediator belonging to the alarmin family, has a key role in different acute and chronic immune disorders. Asthma is a complex disease characterised by recurrent and reversible airflow obstruction associated to airway hyper-responsiveness and airway inflammation.ObjectiveThis literature review aims to analyse advances on HMGB1 role, employment and potential diagnostic application in asthma.MethodsWe reviewed experimental studies that investigated the pathogenetic role of HMGB in bronchial airway hyper-responsiveness, inflammation and the correlation between HMGB1 level and asthma.ResultsA total of 19 studies assessing the association between HMGB1 and asthma were identified.ConclusionsWhat emerged from this literature review was the confirmation of HMGB-1 involvement in diseases characterised by chronic inflammation, especially in pulmonary pathologies. Findings reported suggest a potential role of the alarmin in being a stadiation method and a marker of therapeutic efficacy; finally, inhibiting HMGB1 in humans in order to contrast inflammation should be the aim for future further studies.

show abstract

Section: Resultsmentioning

confidence: 99%

Association between HMGB1 and asthma: a literature review

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Some studies have demonstrated the contribution of PI3K family to the activation of caspase-1 cleavage and IL-1 secretion using different stimuli, although without a correlation specifically to the isoform PI3K . 29,30 The known factors in MSU-induced inflammasome activation include ROS production and potassium efflux. 31,32 Previously, we demonstrated that macrophages and joint tissue stimulated with of MSU crystals produce LTB 4 before the release of active IL-1 .…”

Section: F I G U R E 4 Pi3k Regulates Leukocyte Adhesion and Neutrophmentioning

confidence: 99%

Phosphoinositide-3 kinase gamma regulates caspase-1 activation and leukocyte recruitment in acute murine gout

Tavares

Galvão

Costa

et al. 2019

Journal of Leukocyte Biology

View full text Add to dashboard Cite

This study investigates the participation of PI3Kγ in the development of joint inflammation and dysfunction in an experimental model of acute gout in mice. Acute gout was induced by injection of monosodium urate (MSU) crystals into the tibiofemoral joint of mice. The involvement of PI3Kγ was evaluated using a selective inhibitor and mice deficient for PI3Kγ (PI3Kγ−/−) or with loss of kinase activity. Neutrophils recovered from the inflamed joint were quantified and stained for phosphorylated Akt (pAkt) and production of reactive oxygen species (ROS). The adherence of leukocytes to the joint microvasculature was assessed by intravital microscopy and cleaved caspase‐1 by Western blot. Injection of MSU crystals induced massive accumulation of neutrophils expressing phosphorylated Akt. In the absence of PI3Kγ, there was reduction of pAkt expression, chemokine production, and neutrophil recruitment. Genetic or pharmacological inhibition of PI3Kγ reduced the adherence of leukocytes to the joint microvasculature, even in joints with established inflammation. Neutrophils from PI3Kγ−/− mice produced less ROS than wild‐type neutrophils. There was decreased joint damage and dysfunction in the absence of PI3Kγ. In addition, in the absence of PI3Kγ activity, there was reduction of cleaved caspase‐1 and IL‐1β production in synovial tissue after injection of MSU crystals and leukotriene B4. Our studies suggest that PI3Kγ is crucial for MSU crystal–induced acute joint inflammation. It is necessary for regulating caspase‐1 activation and for mediating neutrophil migration and activation. Drugs that impair PI3Kγ function may be useful to control acute gout inflammation.

show abstract

“…Isocyanates is a group of reactive low-molecular weight chemicals commonly utilized in the manufacturing of polyurethane foams, paints, coatings, elastomers, adhesives, and many other products [1,2,3,4]. In the last 50 years, the production and use of isocyanates have rapidly increased.…”

Section: Background and Aimsmentioning

confidence: 99%

Vitamin E Effect in a Rat Model of Toluene Diisocyanate-Induced Asthma

Muti

Pârvu

Muti

et al. 2016

Medicine and Pharmacy Reports

View full text Add to dashboard Cite

Background and aimThe aim of the study was to evaluate vitamin E effect upon oxidative stress associated with toluene −2, 4-diisocyanate (TDI)-induced asthma in rats.MethodsThe five study groups were: control, vehicle, TDI, vehicle+E, TDI+E. TDI animals were sensitized by nasal administration of TDI 10% (5μl/nostril) between days 1–7 and 15–21. Between days 22–28 groups TDI+E and vehicle+E rats received vitamin E (50 mg/kg, i. v.), and control, vehicle and TDI groups received saline solution. On day 29 the rats were challenged by intranasal application of 5% TDI (5 μl/nostril). On day 30 blood, BALF and lung biopsy were harvested. Oxidative stress tests were malondialdehyde (MDA), protein carbonyls (PC), total thiols (tSH), 1,1-diphenyl-2-picryl hydrazyl (DPPH) and reduced glutathione (GSH).ResultsTDI sensitization increased oxidative stress systemically, but also locally in the respiratory airways and lung tissue. There was an increase of MDA and PC formation associated with a deficiency of the antioxidant defense reflected by DPPH decreases. There were no differences between systemic and local lung concentrations of oxidized molecules.After vitamin E treatment oxidative stress was reduced mostly due to serum, BALF and lung tissue GSH and DPPH increase.ConclusionThe study showed that in rat TDI-induced asthma there was oxidative stress caused by increased ROS production and antioxidants deficiency, and vitamin E reduced ROS production and improved antioxidant defense.

show abstract

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

Cited by 36 publications

References 49 publications

Association between HMGB1 and asthma: a literature review

Association between HMGB1 and asthma: a literature review

Phosphoinositide-3 kinase gamma regulates caspase-1 activation and leukocyte recruitment in acute murine gout

Vitamin E Effect in a Rat Model of Toluene Diisocyanate-Induced Asthma

Contact Info

Product

Resources

About