IL-1 and IL-1 receptor antagonist regulation during keratinocyte cell cycle and differentiation in normal and psoriatic epidermis

Craig Hammerberg, Zsuzsanna Bata-Csorgo, J. J. Voorhees, Kevin D. Cooper

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Changes in the levels of IL-1 (IL-1α, IL-1β, and its receptor antagonist, IL-1RA) occur upon keratinocyte differentiation in vitro and are associated in vivo with abnormal differentiated and hyperproliferative states of psoriatic keratinocytes. A flow cytometric procedure, capable of detecting changes in the intracellular levels of IL-1, was used to determine whether intracellular IL-1/IL-1RA levels in psoriatic and normal keratinocytes alter during in vivo differentiation and the cell cycle. Increases in the IL-1RA levels and IL-1α levels were observed as both normal and psoriatic keratinocytes differentiated from basal stem cells (β1 integrin+, small size) into transient amplifying cells (TAC; β1 integrin+, large size). Upon further differentiation (β1 integrin-, large size) both IL-1RA and IL-1α levels dropped. However, while psoriatic IL-1β levels increased as cells differentiated into TACs, little change occurred in the IL-1β levels of normal keratinocytes during differentiation. Changes in IL-1/IL-1RA levels were also detected as keratinocytes progressed through the cell cycle. Within the basal stem cell population of both normal and psoriatic keratinocytes, the IL-1α and IL-1RA levels increased between G0/G1 and S but not between S and G2/M. However, psoriatic basal keratinocyte IL-1β levels differed from those of normal keratinocytes by showing no increase between S and G2/M. The IL-1/IL-1RA levels of normal TAC increased throughout the cell cycle. However, in psoriatic TAC, a slight decrease in IL-1α and IL-1RA levels was observed between G0/G1 and S followed by a delayed increase between S and G2/M. IL-1β levels in psoriatic TAC varied little throughout the cell cycle. Thus, we were able to detect precisely the regulation of IL-1/IL-1RA intracellular levels during the keratinocyte cell cycle and differentiation, showing notably decreased IL-1β upregulation in psoriatic keratinocytes progressing through the cell cycle.

Original languageEnglish
Pages (from-to)367-374
Number of pages8
JournalArchives of Dermatological Research
Volume290
Issue number7
DOIs
Publication statusPublished - Sep 14 1998

Keywords

  • Cell cycle
  • Differentiation
  • IL-1
  • Psoriasis
  • TGFβ

ASJC Scopus subject areas

  • Dermatology

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