The Flavonoid Luteolin inhibits Fcc-dependent respiratory burst in granulocytes, but not skin blistering in a new model of pemphigoid in adult mice
06.02.2012
Oswald E, Sesarman A, Franzke CW, Wölfle U, Bruckner-Tuderman L, Jakob T, Martin SF, Sitaru C
PLoS One 2012, 7, 12 e31066
Bullous pemphigoid is an autoimmune blistering skin disease associated with autoantibodies against the dermal-epidermal junction. Passive transfer of antibodies against BP180/collagen (C) XVII, a major hemidesmosomal pemphigoid antigen, into neonatal mice results in dermal-epidermal separation upon applying gentle pressure to their skin, but not in spontaneous skin blistering. In addition, this neonatal mouse model precludes treatment and observation of diseased animals beyond 2–3 days. Therefore, in the present study we have developed a new disease model in mice reproducing the spontaneous blistering and the chronic course characteristic of the human condition. We further used this new experimental model to investigate the therapeutic potential of luteolin, a plant flavonoid with potent anti- inflammatory and anti-oxidative properties and good safety profile, in experimental BP. Luteolin inhibited the Fc?-dependent respiratory burst in immune complex-stimulated granulocytes and the autoantibody-induced dermal- epidermal separation in skin cryosections, but was not effective in suppressing the skin blistering in vivo. These studies establish a robust animal model that will be a useful tool for dissecting the mechanisms of blister formation and will facilitate the development of more effective therapeutic strategies for managing pemphigoid diseases.
