Methamphetamine cytotoxicity and effect on LPS-stimulated IL-1beta production by human monocytes.
Methamphetamine (METH) abuse is associated with "METH mouth", characterized by rampant dental decay and destruction of periodontal bone and soft tissues. In periodontitis, monocyte/macrophages, stimulated by bacterial lipopolysaccharide (LPS), produce interleukin-1beta (IL-1beta), contributing to bone and soft tissue degradation. Effects of METH on monocyte/macrophages and its role in periodontitis are unknown. The objective of this study was to determine METH cytotoxicity and effects on constitutive and LPS-stimulated IL-1beta production in THP-1 human monocytes. METH significantly reduced cell viability, assessed by activity of a mitochondrial enzyme, by 20-40% after 24h, with recovery at longer periods. Brief exposure to METH caused <10% cytotoxicity (measured by an assay that detects membrane damage). LPS from E. coli or the periodontopathogen Fusobacterium nucleatum (F. n.) significantly increased IL-1beta production (measured by ELISA). Despite cytotoxicity of some METH concentrations, METH had no significant effect on constitutive IL-1beta production. However, METH generally increased LPS-stimulated IL-1beta levels, reaching statistical significance at 5x10(-5)M METH ( approximately 50% to >100% increase). The study suggests that METH potentiation of periodontopathogen LPS stimulation of IL-1beta in monocytes could contribute to periodontitis in METH abusers, consistent with other studies suggesting a role for increased IL-1beta in deleterious effects of METH.
Tipton
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Department of Bioscience Research, College of Dentistry, The University of Tennessee Health Science Center, 62 South Dunlap Street, Memphis, TN 38163, USA. dtipton@uthsc.edu
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Dabbous
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D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D004926:Escherichia coli / Q000737:chemistry; D016967:Fusobacterium nucleatum / Q000737:chemistry; D006801:Humans; D053583:Interleukin-1beta / Q000096:biosynthesis*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008694:Methamphetamine / Q000633:toxicity*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D010518:Periodontitis / Q000139:chemically induced / Q000473:pathology
D000697:Central Nervous System Stimulants; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D008694:Methamphetamine; D007770:L-Lactate Dehydrogenase