Hexavalent chromium induced ROS formation, Akt, NF-kappaB, and MAPK activation, and TNF-alpha and IL-1alpha production in keratinocytes

Toxicol Lett. 2010 Oct 5;198(2):216-24. doi: 10.1016/j.toxlet.2010.06.024. Epub 2010 Jul 7.

Abstract

In certain cell types, it has been found that, hexavalent chromium could increase ROS formation, activate cell signaling and stimulate the release of cytokines. But, in keratinocytes, these effects have not yet fully been demonstrated. Our aim is to observe the above effects of hexavalent chromium on keratinocytes. By utilizing HaCaT cells and the skin of albino guinea pigs, we showed that hexavalent chromium could increase ROS formation, activate the Akt, NF-kB, and MAPK pathways as well as increase the production of cytokines, including TNF-alpha and IL-1alpha. The release of these cytokines from keratinocytes is considered to be a key participant in the pathogenesis of contact hypersensitivity. Among cement workers, chromium hypersensitivity is an important occupational skin disease issue. Therefore, the observations of our study help us better understand the role of hexavalent chromium on the development of chromium hypersensitivity, which might provide clues for clinicians in the development of chemopreventative agents for the prevention of chromium hypersensitivity among cement workers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Survival / drug effects
  • Chromium / toxicity*
  • Cytokines / biosynthesis
  • Cytokines / metabolism*
  • Dermatitis, Contact / etiology
  • Dermatitis, Contact / immunology
  • Dermatitis, Contact / metabolism
  • Dose-Response Relationship, Drug
  • Environmental Pollutants / toxicity*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Guinea Pigs
  • Humans
  • Hydrogen Peroxide / metabolism
  • Interleukin-1 / biosynthesis
  • Interleukin-1 / metabolism
  • Keratinocytes / drug effects*
  • Keratinocytes / enzymology
  • Keratinocytes / immunology
  • Keratinocytes / metabolism
  • Mitogen-Activated Protein Kinases / metabolism*
  • NF-kappa B / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction
  • Skin / drug effects
  • Skin / immunology
  • Skin / metabolism
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Cytokines
  • Environmental Pollutants
  • Interleukin-1
  • NF-kappa B
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • Chromium
  • chromium hexavalent ion
  • Hydrogen Peroxide
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases