title: Regulation of gene expression by tobacco product preparations in cultured human dermal fibroblasts.
abstract: Skin fibroblasts comprise the first barrier of defense against wounds, and tobacco products directly contact the oral cavity. Cultured human dermal fibroblasts were exposed to smokeless tobacco extract (STE), total particulate matter (TPM) from tobacco smoke, or nicotine at concentrations comparable to those found in these extracts for 1h or 5h. Differences were identified in pathway-specific genes between treatments and vehicle using qRT-PCR. At 1h, IL1α was suppressed significantly by TPM and less significantly by STE. Neither FOS nor JUN was suppressed at 1h by tobacco products. IL8, TNFα, VCAM1, and NFκB1 were suppressed after 5h with STE, whereas only TNFα and NFκB1 were suppressed by TPM. At 1h with TPM, secreted levels of IL10 and TNFα were increased. Potentially confounding effects of nicotine were exemplified by genes such as ATF3 (5h), which was increased by nicotine but suppressed by other components of STE. Within 2h, TPM stimulated nitric oxide production, and both STE and TPM increased reactive oxygen species. The biological significance of these findings and utilization of the gene expression changes reported herein regarding effects of the tobacco product preparations on dermal fibroblasts will require additional research.
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA. Electronic address: gloria.malpass@gmail.com.
authors.forename: Gloria E
authors.initials: GE
authors.lastname: Malpass
authors.affiliation: Department of Microbiology and Immunology, Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA. Electronic address: sarimill@wakehealth.edu.
authors.forename: Subhashini
authors.initials: S
authors.lastname: Arimilli
authors.affiliation: R&D Department, R.J. Reynolds Tobacco Company, Winston-Salem, NC 27102, USA. Electronic address: prasadg@rjrt.com.
authors.forename: G L
authors.initials: GL
authors.lastname: Prasad
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA. Electronic address: ahowlett@wakehealth.edu.
authors.forename: Allyn C
authors.initials: AC
authors.lastname: Howlett
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003872:Dermatitis / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D017781:Genes, Immediate-Early; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D009538:Nicotine / Q000633:toxicity*; D018722:Nicotinic Agonists / Q000633:toxicity*; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D062789:Tobacco Products / Q000633:toxicity*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D018722:Nicotinic Agonists; D012333:RNA, Messenger; D014028:Tobacco Smoke Pollution; D013481:Superoxides; D009569:Nitric Oxide; D009538:Nicotine
keywords: Interleukin-8; Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1; Pro-inflammatory cytokines; Tobacco product preparations; Tumor necrosis factor alpha; Vascular cell adhesion molecule 1