title: The increases in relative mRNA expressions of inflammatory cytokines and chemokines in splenic macrophages from rats exposed to multi-walled carbon nanotubes by whole-body inhalation for 13 weeks.
abstract: BACKGROUND
  The toxicity of multi-walled carbon nanotubes (MWCNT) may be related to the immune system. The objective of this study was to obtain information for immunotoxic mechanisms of MWCNT in situ.
  
  
  METHODS
  Using whole-body inhalation, male and female rats were exposed to 0, 0.2, 1 or 5 mg MWCNT/m³ for 13 weeks. Thereafter, spleens were recovered from the rats. Real-time PCR was done to assess expression of TNFα, IL-1β, IL-6, IL-10, MCP-1 and MIP-1α mRNA in the splenic macrophages; splenic T-lymphocytes were examined for IL-2 and TGF-β1 mRNA expression.
  
  
  RESULTS
  The relative expression of IL-1β mRNA in the cells from female rats exposed to 5 mg MWCNT/m³ was significantly higher than that in control cells. For IL-6 and IL-10, cells from rats in the 0.2 and 5 mg MWCNT/m³ had significantly higher mRNA expressions than did cells from controls. Expression of IL-1β, IL-6 and TNFα genes in cells from males in all exposure groups were higher than in control cells. Expression of MIP-1α in the cells from female 5-mg group was significantly higher than that in cells in the control. Only IL-2 was expression reduced, i.e. cells from male and female rats in all MWCNT groups had significantly lower mRNA expressions than control cells.
  
  
  CONCLUSIONS
  Systemic inflammation would likely occur in rats (or other hosts) exposed to MWCNT via inhalation due to increases in the expression of inflammatory cytokines in splenic macrophages. Moreover, decreases in IL-2 expression in T-lymphocytes may be critical to the potential reductions in anti-tumor responses in MWCNT-exposed hosts.
authors.affiliation: Department of Public Health and Environmental Medicine, Jikei University School of Medicine , Shinbashi, Tokyo , Japan .
authors.forename: Takamasa
authors.initials: T
authors.lastname: Kido
authors.forename: Masashi
authors.initials: M
authors.lastname: Tsunoda
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kasai
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sasaki
authors.forename: Yumi
authors.initials: Y
authors.lastname: Umeda
authors.forename: Hideki
authors.initials: H
authors.lastname: Senoh
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yanagisawa
authors.forename: Masumi
authors.initials: M
authors.lastname: Asakura
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Aizawa
authors.forename: Shoji
authors.initials: S
authors.lastname: Fukushima
mesh_terms: D000336:Aerosols; D000465:Algorithms; D000818:Animals; D002478:Cells, Cultured; D018925:Chemokines / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D007249:Inflammation / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019570:Inhalation Exposure / Q000009:adverse effects*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D037742:Nanotubes, Carbon / Q000032:analysis / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D011916:Rats, Inbred F344; D013154:Spleen / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014018:Tissue Distribution; D059550:Toxicity Tests, Subchronic; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D000336:Aerosols; D018925:Chemokines; D016207:Cytokines; D037742:Nanotubes, Carbon; D012333:RNA, Messenger
keywords: Cytokines; immunotoxicology; multi-walled carbon nanotube; occupational health; rat