Standardized tape stripping prior to patch testing induces upregulation of Hsp90, Hsp70, IL-33, TNF-α and IL-8/CXCL8 mRNA: new insights into the involvement of 'alarmins'.
BACKGROUND
The strip patch test is recommended if patch test results are presumed to be false-negative. It is under discussion whether the cutaneous inflammation induced by tape stripping is a pivotal element in enhancing the allergic contact dermatitis response.


OBJECTIVE
To investigate epidermal mRNA expression of mediators implicated in the regulation of inflammation induced by tape stripping according to our standardized protocol in human skin.


METHODS
Thirty-one healthy volunteers (median age 26 years, range 18-62 years) participated in the study. We measured epidermal mRNAs coding for cytokines [tumour necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin (IL)-1α, IL-1β, IL-33, IL-10, IL-8/CXCL8, chemokine (C-C motif) ligand 2 (CCL2)/MCP-1 (monocyte chemotactic protein-1), chemokine (C-C motif) ligand 5 (CCL5)/RANTES (regulated upon activation normal T-cell expressed, and presumably secreted), IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF)], an adhesion molecule [intercellular adhesion molecule type 1 (ICAM-1)], heat shock proteins (Hsp27, Hsp70 and Hsp90), and the inflammasome complex [NACHT-LRR-PYD-containing protein-3 (NALP3), apoptosis-associated speck-like protein containing a CARD (ASC)/CARD5 (caspase recruitment domain-containing protein-5) and caspase-1] in tape-stripped skin of the upper back relative to untreated skin of the upper back, using quantitative real-time reverse transcription polymerase chain reaction technology.


RESULTS
Epidermal mRNA expression levels of TNF-α, Hsp90, Hsp70, IL-33, and IL-8/CXCL8 were significantly upregulated, whereas CCL5/RANTES expression was significantly downregulated 6 hr after standardized tape stripping.


CONCLUSIONS
Tape stripping the skin according to our standardized protocol shows immunostimulatory effects, with induction of keratinocyte-derived 'alarmins' and cytokines mounting an immune response, which may contribute to the increased sensitivity of the strip patch test versus the patch test.
Dickel
Heinrich
H
Department of Dermatology, Ruhr University Bochum, Bochum, Germany. h.dickel@klinikum-bochum.de
Gambichler
Thilo
T
Kamphowe
Jeanette
J
Altmeyer
Peter
P
Skrygan
Marina
M
D000293:Adolescent; D000328:Adult; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D020170:Caspase 1 / Q000096:biosynthesis / Q000235:genetics; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D018946:Chemokine CCL5 / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics; D004817:Epidermis / Q000276:immunology / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics; D055551:HSP27 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D018841:HSP90 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D006360:Heat-Shock Proteins; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D000067596:Interleukin-33; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D007378:Interleukins / Q000096:biosynthesis* / Q000235:genetics; D015603:Keratinocytes / Q000378:metabolism; D008875:Middle Aged; D018832:Molecular Chaperones; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010328:Patch Tests / Q000379:methods*; D014176:Protein Biosynthesis / Q000235:genetics*; D012333:RNA, Messenger; D048348:Reverse Transcription; D012269:Ribosomal Proteins / Q000096:biosynthesis / Q000235:genetics; D053832:Surgical Tape; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation; D055815:Young Adult
D053468:CARD Signaling Adaptor Proteins; C111835:CCL2 protein, human; C483024:CCL5 protein, human; C508606:CXCL8 protein, human; D002352:Carrier Proteins; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D016207:Cytokines; D003598:Cytoskeletal Proteins; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; C506536:IL33 protein, human; D000067596:Interleukin-33; D016209:Interleukin-8; D007378:Interleukins; D018832:Molecular Chaperones; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C402202:PYCARD protein, human; D012333:RNA, Messenger; D012269:Ribosomal Proteins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C068468:RPL38 protein, human; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D020170:Caspase 1