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Reactive oxygen species in tumor necrosis factor-alpha-activated primary human keratinocytes: implications for

Chen N Young1, Jay I Koepke2, Laura J Terlecky3

  • 1Department of Dermatology, Wayne State University School of Medicine, Detroit, Michigan, USA.

The Journal of Investigative Dermatology
|May 9, 2008
PubMed

Insights

Tumor necrosis factor-alpha (TNF-alpha) rapidly triggers reactive oxygen species (ROS) and inflammatory cytokine production in human skin cells. Antioxidants like catalase show promise in treating inflammatory skin diseases such as psoriasis.

Area of Science:

  • Dermatology
  • Immunology
  • Cell Biology

Background:

  • Tumor necrosis factor-alpha (TNF-alpha) is a key cytokine in skin inflammation.
  • Reactive oxygen species (ROS) are implicated in TNF-alpha signaling, but their role in keratinocytes is unclear.
  • Primary human keratinocytes serve as a model for inflammatory skin diseases like psoriasis.

Purpose of the Study:

  • To investigate the role of ROS in TNF-alpha signaling pathways in human keratinocytes.
  • To elucidate the mechanisms of TNF-alpha-induced inflammatory cytokine production.
  • To explore the therapeutic potential of antioxidants in inflammatory skin conditions.

Main Methods:

  • In vitro and in cellulo experiments using primary human keratinocytes.
  • Analysis of TNF-alpha-induced ROS generation, IkappaB degradation, and NF-kappaB p65 nuclear translocation.
  • Assessment of cytokine production and the effects of antioxidants (catalase, taurine, N-acetyl-cysteine).

Main Results:

  • TNF-alpha rapidly induced ROS generation, IkappaB degradation, NF-kappaB p65 nuclear translocation, and inflammatory cytokine production.
  • TNF-alpha-induced cytokine production was mediated by mammalian target of rapamycin (mTOR) signaling via NF-kappaB and by ROS.
  • TNF-alpha-dependent NF-kappaB activation was independent of ROS.
  • Antioxidants attenuated TNF-alpha-induced cytokine production.

Conclusions:

  • ROS play a significant role in TNF-alpha-induced inflammatory cytokine production in keratinocytes.
  • TNF-alpha signaling involves both NF-kappaB and ROS-dependent pathways.
  • Antioxidants, particularly catalase, show potential for treating inflammatory skin diseases like psoriasis.

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