Acute exposure to methamphetamine alters TLR9-mediated cytokine expression in human macrophage

• Published in: Immunobiology (1979) Vol. 221; no. 2; pp. 199 - 207
• Main Authors: Burns, Ariel, Ciborowski, Pawel
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier GmbH 01.02.2016
• Subjects: Advanced Basic Science; Allergy and Immunology; CCL7; Cell Line; Central Nervous System Stimulants - pharmacology; Chemokine CCL7 - genetics; Chemokine CCL7 - immunology; Chemokine CXCL1 - genetics; Chemokine CXCL1 - immunology; Chemokine CXCL16; Chemokines, CXC - genetics; Chemokines, CXC - immunology; Cytokine; Gene Expression Profiling; Gene Expression Regulation; Humans; Immunity, Innate; Inflammation; Interleukin-8 - genetics; Interleukin-8 - immunology; Macrophage; Macrophages - cytology; Macrophages - drug effects; Macrophages - immunology; Methamphetamine; Methamphetamine - pharmacology; Myeloid Differentiation Factor 88 - genetics; Myeloid Differentiation Factor 88 - immunology; Receptors, Scavenger - genetics; Receptors, Scavenger - immunology; Signal Transduction - drug effects; Signal Transduction - immunology; Toll-Like Receptor 9 - genetics; Toll-Like Receptor 9 - immunology; Toll-like receptor signaling; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - immunology; Toll-like receptor signaling; Inflammation; CCL7; Methamphetamine; Cytokine; Macrophage
• ISSN: 0171-2985; 1878-3279
• DOI: 10.1016/j.imbio.2015.09.006

Abstract Recent studies show that methamphetamine (Meth) use leads to higher susceptibility to and progression of infections, which suggests impairment of the immune system. The first line of defense against infections is the innate immune system and the macrophage is a key player in preventing and fighting infections. So we profiled cytokines over time in Meth treated THP-1 cells, as a human macrophage model, at a relevant concentration using high throughput screening to find a signaling target. We showed that after a single exposure, the effect of Meth on macrophage cytokine production was rapid and time dependent and shifted the balance of expression of cytokines to pro-inflammatory. Our results were analogous to previous reports in that Meth up-regulates TNF-α and IL-8 after two hours of exposure. However, global screening led to the novel identification of CXCL16, CXCL1 and many other up-regulated cytokines. We also showed CCL7 as the most down-regulated chemokine due to Meth exposure, which led us to hypothesize that Meth dysregulates the MyD88-dependent Toll-like receptor 9 (TLR9) signaling pathway. In conclusion, altered cytokine expression in macrophages suggests it could lead to a suppressed innate immunity in people who use Meth.