title: Tannic acid induces in vitro acantholysis of keratinocytes via IL-1alpha and TNF-alpha.
abstract: The mechanism of acantholysis in pemphigus vulgaris (PV) is an intriguing argument since several chemical mediators are implicated. We previously reported a central role for IL-1alpha and TNF- alpha, both able to regulate complement activation and plasminogen activators. Very little is known about what triggers the disease (drugs, viruses or food). In this study, we evaluate the molecular role of tannins in acantholysis. By HPLC chromatography we measured tannic acid (TA) and gallic acid (GA) in blister fluid of 4 groups of patients divided according to their dietary habits, including a regular diet, a diet rich in tannins, a diet free of tannins, and a group of pemphigus patients. Blister fluid was obtained from patients using a suction blister apparatus. We show that people with a diet rich in tannins have increased tannin metabolites (TA and GA) in the skin in respect to controls (tannin-rich diet: GA = 194.52+/-2.39 nmol/ml; TA = 348.28+/-1.4 nmol/ml versus tannin-Mediterranean diet: GA = 15.28+/-1.63 nmol/ml; TA = 22.81+/-1.68 nmol/ml). PV patients showed similar values to the Mediterranean diet population (PV patients: GA = 95.8+/-1.97 nmol/ml; TA = 199.09+/-4.15 nmol/ml versus Mediterranean diet: GA = 83.53+/-2.35 nmol/ml; TA = 195.1+/-2.50 nmol/ml). In an in vitro acantholysis system using TA and PV-IgG we show that TA 0.1 mM in NHEK culture is able to induce acantholysis. This effect was able to amplify the acantholytic action of PV-IgG in vitro. A blocking study using anti IL-1 alpha and anti TNF-alpha antibodies showed a reduction in TA-induced acantholysis. Taken together, these results suggest that a diet rich in tannins could be a trigger in genetically predisposed patients. If these data are confirmed, a complementary diet poor in tannins may be useful in patients affected by PV.
authors.affiliation: Department of Dermatology, Catholic University of the Sacred Heart, Rome, Italy. feliciani@rm.unicatt.it
authors.forename: C
authors.initials: C
authors.lastname: Feliciani
authors.forename: E
authors.initials: E
authors.lastname: Ruocco
authors.forename: A
authors.initials: A
authors.lastname: Zampetti
authors.forename: P
authors.initials: P
authors.lastname: Toto
authors.forename: Pa
authors.initials: P
authors.lastname: Amerio
authors.forename: A
authors.initials: A
authors.lastname: Tulli
authors.forename: P
authors.initials: P
authors.lastname: Amerio
authors.forename: V
authors.initials: V
authors.lastname: Ruocco
mesh_terms: D000051:Acantholysis / Q000139:chemically induced*; D000328:Adult; D005260:Female; D005707:Gallic Acid / Q000378:metabolism; D006801:Humans; D053582:Interleukin-1alpha / Q000378:metabolism*; D015603:Keratinocytes / Q000187:drug effects*; D008297:Male; D013634:Tannins / Q000378:metabolism / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D053582:Interleukin-1alpha; D013634:Tannins; D014409:Tumor Necrosis Factor-alpha; D005707:Gallic Acid