title: Simvastatin attenuates rhinovirus-induced interferon and CXCL10 secretion from monocytic cells in vitro.
abstract: RV infections frequently trigger exacerbations of respiratory diseases, such as asthma, yet treatment and intervention options remain limited. Statin drugs are the treatment of choice for dyslipidemia and can also modulate immune cell function. To determine whether statin drugs modify antiviral responses of human monocytic cells, we obtained blood monocytes from donors with allergies and/or asthma and treated the cells with sim prior to challenge with RV. RV-induced secretion of CXCL10 was attenuated significantly, irrespective of RV type (RV-16, -14, or -1A), which corresponded with decreases in IFN-α secretion and pSTAT1. Sim pretreatment also reduced RV-induced CXCL10 secretion from human alveolar macrophages. The addition of mev and GGPP-two intermediates of the cholesterol biosynthesis pathway-was able to rescue CXCL10 release fully, demonstrating that effects of sim were related to inhibition of cholesterol biosynthesis and not to an off-target effect. In addition, sim pretreatment attenuated IFN-α-induced pSTAT1 and CXCL10 secretion, providing evidence that sim additionally can affect type I IFNR signaling. SOCS1 and 3 mRNA are both induced with RV stimulation, but sim did not elevate SOCS1 or SOCS3 mRNA expression basally or in the presence of RV. Our findings suggest that sim inhibition of the cholesterol biosynthesis pathway leads to decreased RV-induced chemokine secretion in monocytes and macrophages. These findings suggest that statin drugs have the potential to curb the inflammatory response to RV infection.
authors.affiliation: Departments of Biomolecular Chemistry, Nutritional Sciences, and lisawickert@gmail.com.
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Wickert
authors.affiliation: Departments of Biomolecular Chemistry.
authors.forename: Maya R
authors.initials: MR
authors.lastname: Karta
authors.affiliation: Departments of Biomolecular Chemistry.
authors.forename: Anjon
authors.initials: A
authors.lastname: Audhya
authors.affiliation: Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Gern
authors.affiliation: Departments of Biomolecular Chemistry.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Bertics
mesh_terms: D054357:Chemokine CXCL10 / Q000096:biosynthesis* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D016898:Interferon-alpha / Q000096:biosynthesis*; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D012229:Rhinovirus / Q000276:immunology*; D050794:STAT1 Transcription Factor / Q000097:blood; D019821:Simvastatin / Q000494:pharmacology*; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000502:physiology
chemical_list: C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016898:Interferon-alpha; C108944:SOCS1 protein, human; C106644:SOCS3 protein, human; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D019821:Simvastatin
keywords: chemokines; inflammation; macrophages; statins; virus