ArticleJournal of neuroinflammation2012
Regulatory effects of the JAK3/STAT1 pathway on the release of secreted phospholipase A₂-IIA in microvascular endothelial cells of the injured brain.
Article in Journal of neuroinflammation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- sPLA2-IIA modifies progranulin deficiency phenotypes in mouse models.Molecular neurodegeneration · 2025Article
- PPARδ restrains the suppression function of intra-tumoral Tregs by limiting CIITA-MHC II expression.bioRxiv : the preprint server for biology · 2024Article
- MiR-122 overexpression alleviates oxygen-glucose deprivation-induced neuronal injury by targeting sPLA2-IIA.Frontiers in neurology · 2024Article
- Modulation of Airway Expression of the Host Bactericidal Enzyme, sPLA2-IIA, by Bacterial Toxins.Toxins · 2023Review
- The interaction of secreted phospholipase A2-IIA with the microbiota alters its lipidome and promotes inflammation.JCI insight · 2022Article
- Negative Feedback Role of Astrocytes in Shaping Excitation in Brain Cell Co-cultures.Frontiers in cellular neuroscience · 2021Article
- JANEX-1 improves acute pulmonary embolism through VEGF and FAK in pulmonary artery smooth muscle cells.Experimental biology and medicine (Maywood, N.J.) · 2020Article
- The Immunomodulatory Potential of Copper and Silver Based Self-Assembled Metal Organic Biohybrids Nanomaterials in Cancer Theranostics.Frontiers in chemistry · 2020Article
- Tagged Halloysite Nanotubes as a Carrier for Intercellular Delivery in Brain Microvascular Endothelium.Frontiers in bioengineering and biotechnology · 2020Article
- Brain injury results in lower levels of melatonin receptors subtypes MT1 and MT2.Neuroscience letters · 2017Article
- Severe Cranioencephalic Trauma: Prehospital Care, Surgical Management and Multimodal Monitoring.Bulletin of emergency and trauma · 2016Review
- Transcriptome-wide RNA sequencing analysis of rat skeletal muscle feed arteries. I. Impact of obesity.Journal of applied physiology (Bethesda, Md. : 1985) · 2014Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSecreted phospholipase A₂-IIA (sPLA₂-IIA) is an inducible enzyme released under several inflammatory conditions. It has been shown that sPLA₂-IIA is released from rat brain astrocytes after inflammatory stimulus, and lipopolysaccharide (LPS) and nitric oxide (NO) have been implicated in regulation of this release. Here, brain microvascular endothelial cells (BMVECs) were treated with LPS to uncover whether sPLA₂-IIA was released, whether nitric oxide regulated this release, and any related signal mechanisms.
methodsSupernatants were collected from primary cultures of BMVECs. The release of sPLA2-IIA, and the expression of inducible nitric oxide synthase (iNOS), phospho-JAK3, phospho-STAT1, total JAK3 and STAT1, β-actin, and bovine serum albumin (BSA) were analyzed by Western blot or ELISA. NO production was calculated by the Griess reaction. sPLA₂ enzyme activity was measured with a fluorometric assay. Specific inhibitors of NO (L-NAME and aminoguanidine, AG), JAK3 (WHI-P154,WHI), STAT1 (fludarabine, Flu), and STAT1 siRNA were used to determine the involvement of these molecules in the LPS-induced release of sPLA₂-IIA from BMVECs. Nuclear STAT1 activation was tested with the EMSA method. The monolayer permeability of BMVECs was measured with a diffusion assay using biotinylated BSA.
resultsTreatment of BMVECs with LPS increased the release of sPLA₂-IIA and nitrite into the cell culture medium up to 24 h. Pretreatment with an NO donor, sodium nitroprusside, decreased LPS-induced sPLA₂-IIA release and sPLA₂ enzyme activity, and enhanced the expression of iNOS and nitrite generation after LPS treatment. Pretreatment with L-NAME, AG, WHI-P154, or Flu notably reduced the expression of iNOS and nitrite, but increased sPLA₂-IIA protein levels and sPLA₂ enzyme activity. In addition, pretreatment of the cells with STAT1 siRNA inhibited the phosphorylation of STAT1, iNOS expression, and nitrite production, and enhanced the release of sPLA₂-IIA. Pretreatment with the specific inhibitors of NOS, JAK₂, and STAT3 decreased the permeability of BMVECs. In contrast, inhibition of sPLA₂-IIA release increased cell permeability. These results suggest that sPLA₂-IIA expression is regulated by the NO-JAK3-STAT1 pathway. Importantly, sPLA₂-IIA augmentation could protect the LPS-induced permeability of BMVECs.
conclusionOur results demonstrate the important action of sPLA₂-IIA in the permeability of microvascular endothelial cells during brain inflammatory events. The sPLA₂ and NO pathways can be potential targets for the management of brain MVEC injuries and related inflammation.
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