Effective attenuation of endotoxin-induced acute lung injury by 2,3-diacetyloxybenzoic acid in two independent animal models

Eiznhamer, David A.; Flavin, Michael T.; Jesmok, Gary; Borgia, Julian F.; Nelson, Deanna J.; Burhop, Kenneth E.; Xu, Z.-S.

doi:10.1016/j.pupt.2003.11.003

Cited by 9 publications

(9 citation statements)

References 24 publications

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“…MLC has been shown to be involved in hypoxia-induced conformational changes in the lung (Eiznhamer et al, 2004) as well as TGF-β-mediated changes through Rho kinase (Clements et al, 2005) leading to breakdown of the alveolar barrier in the lung. Our in vitro data, which show no effect of inhibition of rho kinase on MLCK expression and partial inhibition of MLCK210 induction only at the highest dose of inhibitor, suggest that this pathway does not play a significant role in the albumin-induced increase in MLCK in astrocytes.…”

Section: Discussionmentioning

confidence: 99%

Albumin causes increased myosin light chain kinase expression in astrocytes via p38 mitogen-activated protein kinase

et al. 2011

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Myosin light chain kinase (MLCK) plays an important role in the reorganization of the cytoskeleton leading to disruption of vascular barrier integrity in multiple organs including the blood brain barrier (BBB) after traumatic brain injury (TBI). MLCK has been linked to transforming growth factor (TGF) and rho kinase signaling pathways, but the mechanisms regulating MLCK expression following TBI are not well understood. Albumin leaks into the brain parenchyma following TBI, activates glia and has been linked to TGF-β receptor signaling. We investigated the role of albumin in the increase in MLCK in astrocytes and the signaling pathways involved in this increase. Following midline closed-skull TBI in mice, there was a significant increase in MLCK-immunoreactive (IR) cells and albumin extravasation, which was prevented by treatment with the MLCK inhibitor ML-7. Using immunohistochemical methods, we identified the MCLK-IR cells as astrocytes. In primary astrocytes, exposure to albumin increased both isoforms of MLCK, 130 and 210. Inhibition of the TGF-β receptor partially prevented the albumin-induced increase in both isoforms, which was not prevented by inhibition of smad3. Inhibition of p38 MAPK, but not ERK, JNK or rho kinase also prevented this increase. These results are further evidence of a role of MCLK in the mechanisms of BBB compromise following TBI, and identify astrocytes as a cell type, in addition to endothelium in the BBB which express MLCK. These findings implicate albumin, acting through p38 MAPK, in a novel mechanism by which activation of MLCK following TBI may lead to compromise of the BBB. Keywords myosin light chain kinase; blood brain barrier; astrocyte; traumatic brain injury; transforming growth factor

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Section: Discussionmentioning

confidence: 99%

Albumin causes increased myosin light chain kinase expression in astrocytes via p38 mitogen-activated protein kinase

et al. 2011

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“…DABA was designed as a pro-drug of 2,3-dihydroxybenzoic acid (DHBA) to increase its lipophilicity and thus increase its intracellular delivery [230]. DHBA is an old drug known by its strong iron chelation activity for a long time [231].…”

Section: Chapter 4 Adjunctive Immunomodulator Therapy Improves Mortamentioning

confidence: 99%

“…Early systemic treatment by DABA before and after endotoxin administration could significantly decrease lung microvascular permeability [230]. Therefore, we sought to test if adjunctive DABA therapy would also prevent the increased lung immunopathology associated with antibiotic treatment of SBP.…”

Section: Chapter 4 Adjunctive Immunomodulator Therapy Improves Mortamentioning

confidence: 99%

“…The injection solution was kept at 4°C and was used within 1-2 days. Mice were i.p injected with DABA in the same dose as used before for treating acute lung injury (150 mg/kg/day) [230], but following the same regimen as dexamethasone.…”

Section: 3-diacetyloxybenzoic Acid Treatment Regimenmentioning

confidence: 99%

“…We also tested the efficacy of DABA, a novel immunomodulator that was shown to attenuate endotoxin-induced acute lung injury [230]. Combined DABA therapy with ampicillin treatment of SBP demonstrated protective effect similar to that of dexamethasone.…”

Section: Treatment Strategies Of Secondary Bacterial Pneumonia Followmentioning

confidence: 99%

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Tetrahydrocoptisine Protects Rats from LPS-Induced Acute Lung Injury

et al. 2014

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Recent studies show that nuclear factor-kappa B (NF-κB) signaling pathway plays a key role in contributing to the development of lipopolysaccharide (LPS)-induced acute lung injury (ALI). Tetrahydrocoptisine is one of the main active components of Chelidonium majus L. and has been described to be effective in suppressing inflammation. The aim of the present study is to evaluate the protective effect of tetrahydrocoptisine on LPS-induced ALI in rats and clarify its underlying mechanisms of action. We found that in vivo pretreatment with tetrahydrocoptisine to rats 30 min before inducing ALI by LPS markedly decreased the mortality rate, lung wet weight to dry weight ratio, and ameliorated lung pathological changes. Meanwhile, tetrahydrocoptisine significantly inhibited the increase of the amounts of inflammatory cells, total protein content, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) secretion in the bronchoalveolar lavage fluids (BALFs). Furthermore, tetrahydrocoptisine inhibited myeloperoxidase (MPO) accumulation in lung tissue and alleviated TNF-α and IL-6 production in serum. Additionally, immunohistochemistry showed that tetrahydrocoptisine efficiently reduced nuclear factor-kappa B (NF-κB) activation by inhibiting the translocation of NF-κBp65. In conclusion, our results demonstrate that tetrahydrocoptisine possesses a protective effect on LPS-induced ALI through inhibiting of NF-κB signaling pathways, which may involve the inhibition of pulmonary inflammatory process.

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Effective attenuation of endotoxin-induced acute lung injury by 2,3-diacetyloxybenzoic acid in two independent animal models

Cited by 9 publications

References 24 publications

Albumin causes increased myosin light chain kinase expression in astrocytes via p38 mitogen-activated protein kinase

Albumin causes increased myosin light chain kinase expression in astrocytes via p38 mitogen-activated protein kinase

A Novel Mechanism of Enhanced Susceptibility to Bacterial Pneumonia in Influenza-infected Hosts

Tetrahydrocoptisine Protects Rats from LPS-Induced Acute Lung Injury

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