title: Modulation of innate immune-related pathways in nicotine-treated SH-SY5Y cells.
abstract: Although nicotine has a broad impact on both the central and peripheral nervous systems, the molecular mechanisms remain largely unknown, especially at the signaling pathway level. To investigate that aspect, we employed both conventional molecular techniques, such as quantitative real-time PCR and Western blotting analysis, and high-throughput microarray approach to identify the genes and signaling pathways that are modulated by nicotine. We found 14 pathways significantly altered in SH-SY5Y neuroblastoma cells. Of these, the Toll-like receptor pathway (TLR; p = 2.57 × 10(-4)) is one of the most important innate immune pathways. The death receptor pathway (DR; p = 8.71 × 10(-4)), whose transducers coordinate TLR signals and help conduct the host immune response to infection, was also significantly changed by nicotine. Furthermore, we found that several downstream pathways of TLR and DR signaling, such as PI3K/AKT signaling (p = 9.55 × 10(-6)), p38 signaling (p = 2.40 × 10(-6)), and ERK signaling (p = 1.70 × 10(-4)), were also significantly modulated by nicotine. Interestingly, most of the differentially expressed genes in these pathways leading to nuclear factor κB (NF-κB) activation and those important inhibitors of pathways leading to apoptosis, including FLIP and Bcl-2, were up-regulated by nicotine. Taken together, our findings demonstrate that nicotine can regulate multiple innate immune-related pathways, and our data thus provide new clues to the molecular mechanisms underlying nicotine's regulatory effects on neurons.
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, Peking University, Beijing, China.
authors.forename: Wen-Yan
authors.initials: WY
authors.lastname: Cui
authors.forename: Ju
authors.initials: J
authors.lastname: Wang
authors.forename: Jinxue
authors.initials: J
authors.lastname: Wei
authors.forename: Junran
authors.initials: J
authors.lastname: Cao
authors.forename: Sulie L
authors.initials: SL
authors.lastname: Chang
authors.forename: Jun
authors.initials: J
authors.lastname: Gu
authors.forename: Ming D
authors.initials: MD
authors.lastname: Li
mesh_terms: D017209:Apoptosis; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects* / Q000235:genetics; D007155:Immunologic Factors / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D053218:Receptors, Death Domain / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism; D059467:Transcriptome
chemical_list: D007155:Immunologic Factors; D016328:NF-kappa B; D053218:Receptors, Death Domain; D051193:Toll-Like Receptors; D009538:Nicotine