Epigallocatechin-3-gallate exhibits anti-inflammatory effects in a human interface dermatitis model-implications for therapy.

BACKGROUND: Epigallocatechin-3-gallate (EGCG) has been proven effective in treating viral warts. Since anticarcinogenic as well as anti-inflammatory properties are ascribed to the substance, its use has been evaluated in the context of different dermatoses. The effect of EGCG on interface dermatitis (ID), however, has not yet been explored. OBJECTIVES: In this study, we investigated the effect of EGCG on an epidermal human in vitro model of ID. METHODS: Via immunohistochemistry, lesional skin of lichen planus patients and healthy skin were analysed concerning the intensity of interferon-associated mediators, CXCL10 and MxA. Epidermal equivalents were stained analogously upon ID-like stimulation and EGCG treatment. Monolayer keratinocytes were treated likewise and supernatants were analysed via ELISA while cells were processed for vitality assay or transcriptomic analysis. RESULTS: CXCL10 and MxA are strongly expressed in lichen planus lesions and induced in keratinocytes upon ID-like stimulation. EGCG reduces CXCL10 and MxA staining intensity in epidermis equivalents and CXCL10 secretion by keratinocytes upon stimulation. It furthermore minimizes the cytotoxic effect of the stimulus and downregulates a magnitude of typical pro-inflammatory cytokines that are crucial for the perpetuation of ID. CONCLUSIONS: We provide evidence concerning anti-inflammatory effects of EGCG within a human in vitro model of ID. The capacity to suppress mediators that are centrally involved in disease perpetuation suggests EGCG as a potential topical therapeutic in lichen planus and other autoimmune skin diseases associated with ID.

Anti-inflammatory activity of topical THC in DNFB-mediated mouse allergic contact dermatitis independent of CB1 and CB2 receptors.

BACKGROUND: ∆(9) -Tetrahydrocannabinol (THC), the active constituent of Cannabis sativa, exerts its biological effects in part through the G-protein-coupled CB1 and CB2 receptors, which were initially discovered in brain and spleen tissue, respectively. However, THC also has CB1/2 receptor-independent effects. Because of its immune-inhibitory potential, THC and related cannabinoids are being considered for the treatment of inflammatory skin diseases. Here we investigated the mechanism of the anti-inflammatory activity of THC and the role of CB1 and CB2 receptors. METHODS: We evaluated the impact of topically applied THC on DNFB-mediated allergic contact dermatitis in wild-type and CB1/2 receptor-deficient mice. We performed immunohistochemical analyses for infiltrating immune cells and studied the influence of THC on the interaction between T cells, keratinocytes and myeloid immune cells in vitro. RESULTS: Topical THC application effectively decreased contact allergic ear swelling and myeloid immune cell infiltration not only in wild-type but also in CB1/2 receptor-deficient mice. We found that THC (1) inhibited the production of IFNγ by T cells, (2) decreased the production of CCL2 and of IFNγ-induced CCL8 and CXL10 by epidermal keratinocytes and (3) thereby limited the recruitment of myeloid immune cells in vitro in a CB1/2 receptor-independent manner. CONCLUSIONS: Topically applied THC can effectively attenuate contact allergic inflammation by decreasing keratinocyte-derived pro-inflammatory mediators that orchestrate myeloid immune cell infiltration independent of CB1/2 receptors. This has important implications for the future development of strategies to harness cannabinoids for the treatment of inflammatory skin diseases.