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TARC augments TNF‐α‐induced CTACK production in keratinocytes
Author(s) -
Vestergaard Christian,
Johansen Claus,
Christensen Ulla,
Just Helle,
Hohwy Thomas,
Deleuran Mette
Publication year - 2004
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.0906-6705.2004.00202.x
Subject(s) - ccr4 , ccl17 , chemokine , tumor necrosis factor alpha , scorad , ccr10 , immunology , keratinocyte , medicine , biology , inflammation , psoriasis , chemokine receptor , in vitro , biochemistry , dermatology life quality index
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 Th 2 subtype whereas CTACK attracts skin‐homing T cells of both Th 1 and Th 2 subtype that express CCR10. We found that CTACK can be induced in cultured human keratinocytes by tumor necrosis factor‐α (TNF‐α), 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 Th 2 ‐dominated inflammatory reaction in AD induced by TARC leads to an augmented skin‐specific inflammatory reaction through CTACK.