ArticleTranslational research : the journal of laboratory and clinical medicine2015
Lysophosphatidic acid receptor 1 antagonist ki16425 blunts abdominal and systemic inflammation in a mouse model of peritoneal sepsis.
Article in Translational research : the journal of laboratory and clinical medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
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- Decoding lysophosphatidic acid signaling in physiology and disease: mapping the multimodal and multinodal signaling networks.Signal transduction and targeted therapy · 2025Review
- Preventive effect of small molecule active substances on septic cardiomyopathy after abdominal trauma: a systematic review and meta-analysis.Frontiers in pharmacology · 2025Article
- The role of protein S-acylation in vascular injury associated with metabolic disorders.Frontiers in endocrinology · 2025Review
- Autotaxin Has a Negative Role in Systemic Inflammation.International journal of molecular sciences · 2022Article
- Lysophosphatidic Acid Receptor 3 Suppress Neutrophil Extracellular Traps Production and Thrombosis During Sepsis.Frontiers in immunology · 2022Article
- The novel ORFV protein ORFV113 activates LPA-p38 signaling.PLoS pathogens · 2021Article
- Molecular Regulation of Lysophosphatidic Acid Receptor 1 Maturation and Desensitization.Cell biochemistry and biophysics · 2021Review
- A blocking peptide stabilizes lysophosphatidic acid receptor 1 and promotes lysophosphatidic acid-induced cellular responses.Journal of cellular biochemistry · 2021Article
- Definity, an affinity for painful crisis: a case series describing vaso-occlusive pain crises in sickle cell patients undergoing echocardiogram with Definity contrast.European heart journal. Case reports · 2021Article
- Inhibition of lysophosphatidic acid receptor 1 attenuates neuroinflammation via PGE2/EP2/NOX2 signalling and improves the outcome of intracerebral haemorrhage in mice.Brain, behavior, and immunity · 2021Article
- The Metabolome and Osteoarthritis: Possible Contributions to Symptoms and Pathology.Metabolites · 2018Review
- Candidate Genes as Biomarkers in Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome Based on mRNA Expression Profile by Next-Generation RNA-Seq Analysis.BioMed research international · 2018Article
- Parkin regulates lipopolysaccharide-induced proinflammatory responses in acute lung injury.Translational research : the journal of laboratory and clinical medicine · 2017Article
- Destabilization of Lysophosphatidic Acid Receptor 1 Reduces Cytokine Release and Protects Against Lung Injury.EBioMedicine · 2016Article
- Deficiency or inhibition of lysophosphatidic acid receptor 1 protects against hyperoxia-induced lung injury in neonatal rats.Acta physiologica (Oxford, England) · 2016Article
- Lysophospholipid mediators in the vasculature.Experimental cell research · 2015Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Lysophosphatidic acid (LPA) is a bioactive lipid mediator of inflammation via the LPA receptors 1-6. We and others have previously described proinflammatory and profibrotic activities of LPA signaling in bleomycin- or lipopolysaccharide (LPS)-induced pulmonary fibrosis or lung injury models. In this study, we investigated if LPA signaling plays a role in the pathogenesis of systemic sepsis from an abdominal source. We report here that antagonism of the LPA receptor LPA1 with the small molecule ki16425 reduces the severity of abdominal inflammation and organ damage in the setting of peritoneal endotoxin exposure. Pretreatment of mice with intraperitoneal ki16425 eliminates LPS-induced peritoneal neutrophil chemokine and cytokine production, liver oxidative stress, liver injury, and cellular apoptosis in visceral organs. Mice pretreated with ki16425 are also protected from LPS-induced mortality. Tissue myeloperoxidase activity is not affected by LPA1 antagonism. We have shown that LPA1 is associated with LPS coreceptor CD14 and the association is suppressed by ki16425. LPS-induced phosphorylation of protein kinase C δ (PKCδ) and p38 mitogen-activated protein kinase (p38 MAPK) in liver cells and interleukin 6 production in Raw264 cells are likewise blunted by LPA1 antagonism. These studies indicate that the small molecule inhibitor of LPA1, ki16425, suppresses cytokine responses and inflammation in a peritoneal sepsis model by blunting downstream signaling through the LPA1-CD14-toll-like receptor 4 receptor complex. This anti-inflammatory effect may represent a therapeutic strategy for the treatment of systemic inflammatory responses to infection of the abdominal cavity.
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