Simvastatin regulates non-neuronal cholinergic activity in T lymphocytes via CD11a-mediated pathways.
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Fujii T, Masuyama K, Kawashima K
Simvastatin regulates non-neuronal cholinergic activity in T lymphocytes via CD11a-mediated pathways.
J Neuroimmunol. 2006 Oct;179(1-2):101-7. Epub 2006 Jul 10.
- PubMed ID
- 16828882 [ View in PubMed]
- Abstract
Lymphocyte function associated antigen-1 (LFA-1; CD11a/CD18) is an important mediator of leukocyte migration and T cell activation. We previously showed that antithymocyte globulin stimulates an independent, non-neuronal cholinergic system in T cells via LFA-1-mediated pathways, as evidenced by increases in acetylcholine (ACh) synthesis and choline acetyltransferase (ChAT) mRNA expression. The cholesterol-lowering drug simvastatin inhibits LFA-1 signaling by binding to an allosteric site on CD11a (LFA-1 alpha chain), which leads to immunomodulation. In the present study, we investigated whether simvastatin modulates lymphocytic cholinergic activity in T cells. We found that anti-CD11a monoclonal antibody (mAb) increased ChAT activity, ACh synthesis and release, and expression of ChAT and M5 muscarinic ACh receptor mRNA in MOLT-3 cells, a human leukemic T cell line. Simvastatin abolished these anti-CD11a mAb-induced increases in lymphocytic cholinergic activity in a manner independent of its cholesterol-lowering activity. These results indicate that LFA-1 contributes to the regulation of lymphocytic cholinergic activity via CD11a-mediated pathways, and suggest that simvastatin exerts its immunosuppressive effects in part via modification of lymphocytic cholinergic activity.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Simvastatin Integrin alpha-L Protein Humans UnknownInhibitory allosteric modulatorDetails