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TARC augments TNF-alpha-induced CTACK production in keratinocytes.

Abstract
Thymus- and activation-regulated chemokine (TARC)/CCL17 and cutaneous T cell-attracting chemokine (CTACK)/CCL27 are both pivotal mediators of the inflammatory reaction of atopic dermatitis (AD). TARC attracts CCR4 positive T cells known to be mainly of Th2 subtype whereas CTACK attracts skin-homing T cells of both Th1 and Th2 subtype that express CCR10. We found that CTACK can be induced in cultured human keratinocytes by tumor necrosis factor-alpha (TNF-alpha), but not by TARC alone. However, if the keratinocytes were preincubated with TNF-a for 6 h, TARC was able to augment the CTACK-inducing effect of TNF-a. Performing immunohistochemical stainings, reverse-transcription polymerase chain reaction (RT-PCR), and Western blotting, we found that TNF-a-induced CCR4 mRNA production, but that stimulated as well as non-stimulated keratinocytes expressed CCR4. In order to see if these results had any clinical relevance, we investigated the plasma concentrations of TARC and CTACK from 48 patients suffering from AD. This revealed that TARC and CTACK concentrations in plasma correlate with each other. Surprisingly, p-CTACK correlated inversely with SCORAD scores of the patients, which most likely is due to the treatment the patients received. Our results suggest that the primary Th2-dominated inflammatory reaction in AD induced by TARC leads to an augmented skin-specific inflammatory reaction through CTACK.
AuthorsChristian Vestergaard, Claus Johansen, Ulla Christensen, Helle Just, Thomas Hohwy, Mette Deleuran
JournalExperimental dermatology (Exp Dermatol) Vol. 13 Issue 9 Pg. 551-7 (Sep 2004) ISSN: 0906-6705 [Print] Denmark
PMID15335355 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • CCL17 protein, human
  • CCL27 protein, human
  • CCR4 protein, human
  • Chemokine CCL17
  • Chemokine CCL27
  • Chemokines, CC
  • Inflammation Mediators
  • Receptors, CCR4
  • Receptors, Chemokine
  • Tumor Necrosis Factor-alpha
Topics
  • Adult
  • Biopsy
  • Cells, Cultured
  • Chemokine CCL17
  • Chemokine CCL27
  • Chemokines, CC (genetics, metabolism)
  • Dermatitis, Atopic (immunology, pathology, physiopathology)
  • Gene Expression (immunology)
  • Humans
  • Inflammation Mediators (metabolism)
  • Keratinocytes (cytology, immunology)
  • Receptors, CCR4
  • Receptors, Chemokine (genetics, metabolism)
  • Severity of Illness Index
  • Th2 Cells (physiology)
  • Tumor Necrosis Factor-alpha (pharmacology)

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