Journal
JOURNAL OF INVESTIGATIVE DERMATOLOGY
Volume 141, Issue 11, Pages 2587-+Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jid.2021.04.009
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- Deutsche For-schungsgemeinschaft
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Patients with epidermolysis bullosa acquisita and mucous membrane pemphigoid are often treated with dapsone, which has shown to reduce inflammation and inhibit the release of LTB4 and ROS from neutrophils. Therefore, dapsone may work by inhibiting these processes in these diseases.
Epidermolysis bullosa acquisita and mucous membrane pemphigoid are autoimmune blistering diseases characterized by mucocutaneous blisters elicited by an autoantibody-mediated immune response against specific proteins of the epidermal basement membrane. The antibiotic dapsone is frequently used to treat both diseases, but its therapeutic effectiveness is uncertain, and its mode of action in these diseases is largely unknown. We evaluated the effect of dapsone in antibody transfer mouse models of epidermolysis bullosa acquisita and mucous membrane pemphigoid, which do not allow the drawing of conclusions on clinical treatment regimens but can be instrumental to partially uncover the mode(s) of action of dapsone in these diseases. Dapsone significantly mitigated inflammation in both models, reducing the recruitment of neutrophils into the skin and disrupting their release of leukotriene B-4 (LTB4) and ROS in response to immune complexes. LTB4 has been implicated in numerous diseases, but effective LTB4 inhibitors for clinical use are not available. Our findings indicate that the mode of action of dapsone in these models may be based on the inhibition of LTB4 and ROS release from neutrophils. Moreover, they encourage testing the use of dapsone as an effective, albeit nonspecific, inhibitor of LTB4 biosynthesis in other LTB4-driven diseases.
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