The Expression of Toll-like Receptors in Dermatological Diseases and the Therapeutic Effect of Current and Newer Topical Toll-like Receptor Modulators

Abstract

Toll-like receptors are a group of glycoproteins located mostly in cellular membranes, capable of recognizing certain molecules in exogenous microorganisms and initiating immune responses against them through the activation of several intracellular signaling pathways. Toll-like receptors can be stimulated when an inflammatory reaction is needed for the treatment of conditions, such as viral infections or skin cancer, or can be inhibited when a reduction of inflammation is necessary for the treatment of conditions, such as rheumatoid arthritis, systemic lupus erythematosus, and septic shock. In the human skin, keratinocytes and Langerhans cells are known to express these receptors. Skin conditions where Toll-like receptors are known to be upregulated include acne, psoriasis, atopic dermatitis, syphilis, leprosy, Staphylococcus aureus infections, candidiasis, and herpes simplex and varicella zoster infections. Besides imiquimod, which is the most successful and more studied topical Toll-like receptor-modulating agent to date, other topical agents, such as nicotinamide, all-trans retinoic acid, adapalene, zinc, and sodium tosylchloramide, have also been found to exert some of their action through Toll-like receptors. Recent topical agents, including CBT-SL5 and CpG-ODN, are being evaluated for the treatment of inflammatory acne and skin cancer, respectively, and have demonstrated to be effective in the treatment of those conditions.