title: Methamphetamine increases LPS-mediated expression of IL-8, TNF-α and IL-1β in human macrophages through common signaling pathways.
abstract: The use of methamphetamine (MA) has increased in recent years, and is a major health concern throughout the world. The use of MA has been associated with an increased risk of acquiring HIV-1, along with an increased probability of the acquisition of various sexually transmitted infections. In order to determine the potential effects of MA exposure in the context of an infectious agent, U937 macrophages were exposed to various combinations of MA and bacterial lipopolysaccharide (LPS). Treatment with MA alone caused significant increases in the levels of TNF-α, while treatment with both MA and LPS resulted in significant increases in TNF-α, IL-1β and the chemokine IL-8. The increases in cytokine or chemokine levels seen when cells were treated with both LPS and MA were generally greater than those increases observed when cells were treated with only LPS. Treatment with chemical inhibitors demonstrated that the signal transduction pathways including NF-kB, MAPK, and PI3-Akt were involved in mediating the increased inflammatory response. As discussed in the paper, these pathways appear to be utilized by both MA and LPS, in the induction of these inflammatory mediators. Since these pathways are involved in the induction of inflammation in response to other pathogens, this suggests that MA-exacerbated inflammation may be a common feature of infectious disease in MA abusers.
authors.affiliation: Division of Pharmacology and Toxicology, School of Pharmacy, School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri, United States of America.
authors.forename: Xun
authors.initials: X
authors.lastname: Liu
authors.forename: Peter S
authors.initials: PS
authors.lastname: Silverstein
authors.forename: Vijeta
authors.initials: V
authors.lastname: Singh
authors.forename: Ankit
authors.initials: A
authors.lastname: Shah
authors.forename: Nilofer
authors.initials: N
authors.lastname: Qureshi
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
mesh_terms: D002460:Cell Line; D002467:Cell Nucleus; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D008694:Methamphetamine / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D052002:NF-kappa B p50 Subunit / Q000037:antagonists & inhibitors / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D021381:Protein Transport; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D013876:Thiophenes / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D018836:Inflammation Mediators; D053583:Interleukin-1beta; D016209:Interleukin-8; D008070:Lipopolysaccharides; D052002:NF-kappa B p50 Subunit; C477523:SC 514; D013876:Thiophenes; D014409:Tumor Necrosis Factor-alpha; D008694:Methamphetamine; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases