UVB-induced apoptosis in normal human keratinocytes: Role of the erbB receptor family

Davina A. Lewis, Steven A. Hurwitz, Dan Spandau

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Exposure of human keratinocytes to ultraviolet B (UVB) light leads to the activation of a variety of cell-surface receptors; however, the biologic consequences of these activated receptors are still unclear. It was previously reported that inhibition of cellular tyrosine kinase activity suppressed UVB-dependent effects in human skin. We confirmed that the same suppression of UVB-induced apoptosis occurs in normal human keratinocytes grown in culture. Furthermore, we sought to determine the role of erbB receptor tyrosine kinases in human keratinocytes following UVB irradiation. Using a specific inhibitor of the erbB family of tyrosine kinase receptors, DAPH, we investigated the effects of UVB-dependent activation of these receptors on keratinocyte biology. The addition of DAPH to keratinocytes resulted in the concentration-dependent protection of UVB-induced apoptosis. The protection from apoptosis was not due to the induction of keratinocyte differentiation, the loss of keratinocyte viability, or inhibition of the proliferative potential of keratinocytes by DAPH. The effect of DAPH on apoptosis was specific for UVB as it had no effect on bleomycin-induced apoptosis. Furthermore, the inhibition of UVB-induced apoptosis could also be observed using neutralizing antibodies to either erbB1 or erbB2. Finally, we demonstrated that DAPH could also inhibit UVB-induced apoptosis in an epidermal organotypic model system. These studies suggest an important role for the erbB receptors in UVB-induced apoptosis of human keratinocytes.

Original languageEnglish
Pages (from-to)316-327
Number of pages12
JournalExperimental Cell Research
Volume284
Issue number2
DOIs
StatePublished - Apr 1 2003

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Keratinocytes
Apoptosis
Protein-Tyrosine Kinases
ErbB Receptors
Bleomycin
Receptor Protein-Tyrosine Kinases
Cell Surface Receptors
Ultraviolet Rays
Neutralizing Antibodies
Skin

Keywords

  • Apoptosis
  • ErbB
  • Keratinocytes
  • UVB

ASJC Scopus subject areas

  • Cell Biology

Cite this

UVB-induced apoptosis in normal human keratinocytes : Role of the erbB receptor family. / Lewis, Davina A.; Hurwitz, Steven A.; Spandau, Dan.

In: Experimental Cell Research, Vol. 284, No. 2, 01.04.2003, p. 316-327.

Research output: Contribution to journalArticle

Lewis, Davina A. ; Hurwitz, Steven A. ; Spandau, Dan. / UVB-induced apoptosis in normal human keratinocytes : Role of the erbB receptor family. In: Experimental Cell Research. 2003 ; Vol. 284, No. 2. pp. 316-327.
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