ArticleThe Journal of biological chemistry2014
Neuroendocrine signaling via the serotonin transporter regulates clearance of apoptotic cells.
Article in The Journal of biological chemistry, 2014. 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, 22 citations in OpenAlex.
- Chronic Obstructive Pulmonary Disease and Depression-The Vicious Mental Cycle.Healthcare (Basel, Switzerland) · 2025Review
- Risperidone Decreases Expression of Serotonin Receptor-2A (5-HT2A) and Serotonin Transporter (SERT) but Not Dopamine Receptors and Dopamine Transporter (DAT) in PBMCs from Patients with Schizophrenia.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Impact of plasma 5-hydroxyindoleacetic acid, a serotonin metabolite, on clinical outcome in septic shock, and its effect on vascular permeability.Scientific reports · 2021Article
- Review
- Interactions Between the Serotonergic and Other Neurotransmitter Systems in the Basal Ganglia: Role in Parkinson's Disease and Adverse Effects of L-DOPA.Frontiers in neuroanatomy · 2020Review
- Serotonin Transporter (Frontiers in genetics · 2019Article
- Prescription medication use and antinuclear antibodies in the United States, 1999-2004.Journal of autoimmunity · 2018Article
- Fluoxetine protects against methamphetamine‑induced lung inflammation by suppressing oxidative stress through the SERT/p38 MAPK/Nrf2 pathway in rats.Molecular medicine reports · 2017Article
- Glycogen synthase kinase-3β modulation of glucocorticoid responsiveness in COPD.American journal of physiology. Lung cellular and molecular physiology · 2015Article
- Proteomic and bioinformatics profile of paired human alveolar macrophages and peripheral blood monocytes.Proteomics · 2015Article
- Nucleoside transporter proteins as biomarkers of drug responsiveness and drug targets.Frontiers in pharmacology · 2015Review
- Lack of association between serotonin transporter 5-HTT gene polymorphism and endometriosis in an Italian patient population.Journal of negative results in biomedicine · 2014Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Serotonin (5-hydroxytryptamine; 5-HT) is a CNS neurotransmitter increasingly recognized to exert immunomodulatory effects outside the CNS that contribute to the pathogenesis of autoimmune and chronic inflammatory diseases. 5-HT signals to activate the RhoA/Rho kinase (ROCK) pathway, a pathway known for its ability to regulate phagocytosis. The clearance of apoptotic cells (i.e. efferocytosis) is a key modulator of the immune response that is inhibited by the RhoA/ROCK pathway. Because efferocytosis is defective in many of the same illnesses where 5-HT has been implicated in disease pathogenesis, we hypothesized that 5-HT would suppress efferocytosis via activation of RhoA/ROCK. The effect of 5-HT on efferocytosis was examined in murine peritoneal and human alveolar macrophages, and its mechanisms were investigated using pharmacologic blockade and genetic deletion. 5-HT impaired efferocytosis by murine peritoneal macrophages and human alveolar macrophages. 5-HT increased phosphorylation of myosin phosphatase subunit 1 (Mypt-1), a known ROCK target, and inhibitors of RhoA and ROCK reversed the suppressive effect of 5-HT on efferocytosis. Peritoneal macrophages expressed the 5-HT transporter and 5-HT receptors (R) 2a, 2b, but not 2c. Inhibition of 5-HTR2a and 5-HTR2b had no effect on efferocytosis, but blockade of the 5-HT transporter prevented 5-HT-impaired efferocytosis. Genetic deletion of the 5-HT transporter inhibited 5-HT uptake into peritoneal macrophages, prevented 5-HT-induced phosphorylation of Mypt-1, reversed the inhibitory effect of 5-HT on efferocytosis, and decreased cellular peritoneal inflammation. These results suggest a novel mechanism by which 5-HT might disrupt efferocytosis and contribute to the pathogenesis of autoimmune and chronic inflammatory diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.