Imiquimod, a Toll-like receptor-7 agonist, induces perforin in cytotoxic T lymphocytes in vitro.
Imiquimod (IMQ), an activator of Toll-like receptor-7 (TLR-7), induces by several routes a profound anti-viral and anti-tumor effect in vivo. Physiologically, the immune system is using perforin-containing granules of cytotoxic T lymphocytes (CTL) towards the same biological purpose. This functional synergism prompted our current experiments addressing the question whether IMQ may influence perforin-release and/or induce perforin in CTLs in vitro. In peripheral lymphocytes of healthy and diseased subjects, IMQ induced a significant increase of perforin(+) CTLs within 12h in all experiments performed. This effect was most pronounced in CTLs of patients suffering from atopic dermatitis, a model disorder for subnormal perforin expression: as compared to perforin(+) CTLs detected at time point zero (100%), up to 270% of perforin(+) CTLs were induced by 2.5 microg/ml [corrected] IMQ. Perforin release from peripheral blood CTLs after PMA/ionomycin-stimulation was not influenced significantly by IMQ. Thus, the biological activity of IMQ appears to exceed its previously known functions, inasmuch as it boosts up significantly the perforin-granule system.
Ambach
Andreas
A
Department of Dermatology and Venereology, Otto-von-Guericke-University, Leipziger Strasse 44, D-39120 Magdeburg, Germany. ambach@medizin.uni-magdeburg.de
Bonnekoh
Bernd
B
Nguyen
Myhan
M
Schön
Michael P
MP
Gollnick
Harald
H
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000328:Adult; D000634:Aminoquinolines / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000097:blood / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D000077271:Imiquimod; D015759:Ionomycin / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011956:Receptors, Cell Surface / Q000187:drug effects*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D051199:Toll-Like Receptor 7; D051193:Toll-Like Receptors
D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D011956:Receptors, Cell Surface; C495348:TLR7 protein, human; D051199:Toll-Like Receptor 7; D051193:Toll-Like Receptors; D054353:Perforin; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate; D000077271:Imiquimod