In vitro modulation of TLR-2, CD1d and IL-10 by adapalene on normal human skin and acne inflammatory lesions.
The anti-inflammatory mechanisms of adapalene, a synthetic retinoid used for the treatment of acne patients, are partially understood. They seem particularly related to the modulation of the non-specific immunity. Recent studies have shown that Toll-like receptor (TLR)-2 expression, a receptor of the innate immune system, was increased in acne lesions and could play an essential role in acne-linked inflammation. The aim of our study was to investigate the new mechanisms of the anti-inflammatory activity of adapalene in vitro, and more specifically the modulatory effect of adapalene on the expression of TLR-2, CD1d, a cell surface glycoprotein that plays a role as antigen-presenting molecules and is responsible for the development of cutaneous inflammation, and also on the expression and the secretion of the anti-inflammatory interleukin (IL)-10 cytokine. Both explants of normal human skin and explants of acne patients were incubated with adapalene (10(-7) or 10(-6) M) or the control medium for 24 h. Evaluation of epidermal expression by immunohistochemistry showed a decreased expression of TLR-2 and IL-10 in explants of normal skin and explants of acne with adapalene. On the contrary, adapalene increased CD1d expression in explants of acne patients. Thus, adapalene can modulate the epidermal immune system by increasing the CD1d expression and by decreasing the IL-10 expression by keratinocytes. Moreover, these modulations could increase the interactions between dendritic cells and T lymphocytes and could strengthen the antimicrobial activity against Propionibacterium acnes. The decreased expression of TLR-2 by the keratinocytes can contribute to explain the anti-inflammatory activity of adapalene observed in clinical practice.
Tenaud
Isabelle
I
Department of Dermatology, CHU, Nantes, France.
Khammari
Amir
A
Dreno
Brigitte
B
D000152:Acne Vulgaris / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000068816:Adapalene; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D018949:Antigens, CD1 / Q000378:metabolism*; D055610:Antigens, CD1d; D001706:Biopsy; D002478:Cells, Cultured; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000378:metabolism*; D009281:Naphthalenes / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051195:Toll-Like Receptor 2 / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D009281:Naphthalenes; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D016753:Interleukin-10; D000068816:Adapalene