Tannic Acid Induces in vitro Acantholysis of Keratinocytes via IL-1α and TNF-α

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-la and TNF-a, 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 PVIgG 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-la and anti TNF-a 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.Immunoglobulin-G deposition on desmoglein (Dsg) protein 3, and sometimes Dsg-l, is the main diagnostic criterion for pemphigus vulgaris (PV), and IgG-Dsg linkage is the most important phase in the development of this bullous disease. To date, we do not know which may be the triggering factors able to induce acantholysis in pemphigus.Acantholysis is a morpho functional change of malpighian epithelia which results in the loss of intercellular cohesion and brings cell keratinization to a standstill. Although acantholytic changes may be seen in numerous heterogeneous clinical conditions, the pemphigus group is the mucocutaneous disorder where acantholysis may be considered the histologic

Reviewing putative industrial triggering in pemphigus: cluster of pemphigus in the area near the wastewater treatment plant

“…Phenol derivatives were reported to induce acantholysis both in vitro and in vivo , after topical application and consumption [24, 40, 41]. The role of polyphenolic compounds – tannins, contained in food or water, was suggested in research articles and case reports describing fogo selvagem (“wild fire”) endemic PF [41–45].…”

“…The role of polyphenolic compounds – tannins, contained in food or water, was suggested in research articles and case reports describing fogo selvagem (“wild fire”) endemic PF [41–45]. Such phenol derivatives include liquid diphenyl sulphide [36] and various synthetic phenolic antioxidants (e.g.…”

Pemfigusta Risk Faktörleri

“…Brenner ve arkadaşları genetik yatkınlığı olan bireylerde fenol ve tiyol grubu içeren gıda ve ilaçların pemfigusu tetikleyebileceğini göstermiştir. 17 Felliciani ve arkadaşları tannik asitin invitro akantolizi indüklediğini göste-rerek, tannik asit içeren gıdaların pemfigusu tetikleyebileceğini öne sürm-üştür. 18 Çay, kahve, acı ve baharatlı gıdalar, tiyol, izotiosiyanat, tannik asit ve sülfür içermektedir.…”

Use of Polyphenolic Compounds in Dermatologic Oncology

“…Tannic acid is the main source of the pro-apoptotic agent gallic acid [251], but is considered more potent than ellagic acid [252]. Tannic acid is an antioxidant, anti-inflammatory, and anti-proliferative agent [253–255]. …”

“…Tannic acid’s antioxidant effect [253–255] occurs because it reduces lipid peroxidation, COX-2, inducible nitric oxide synthase (i-NOS), and PCNA expression, increases reduced glutathione, decreases pro-inflammatory cytokines such as IL-6 and NF-κB, and depletes both hydrogen peroxide and xanthine oxidase [253]. Indeed, it is highly likely that these mechanisms are also important in providing tannic acid’s anti-carcinogenic profile.…”