Proteinases play an important role in conditions associated with inflammatory desquamation of the skin like psoriasis, atopic dermatitis and netherton syndrome. Proteinase inhibitors keep their activity under check. Today I read an article [1] about such an inhibitor called LEKTI (lympho-epithelial Kazal-type-related inhibitor) and the corresponding gene SPINK5, mutations of which is responsible for Netherton syndrome. Authors found that domain 6 and domain 15 inhibit 2 key serine proteinases called hK5 and hK7. They also found that domain 15 with 3 disulphide bonds (and not domain 6) also inhibit plasmin. Plasmin is important in the pathogenesis of pemphigus vulgaris which basically is an autoimmune disease [2]. Hence LEKTI domain 15 may be useful in the treatment of pemphigus vulgaris too. The relevance of the fact that drugs with sulfhydryl groups induce pemphigus with respect to the above finding can be explored.
Interested in further exploring LEKTI bioinformatically?

  1. T. Egelrud et al. hK5 and hK7, two serine proteinases abundant in human skin, are inhibited by LEKTI domain 6. British Journal of Dermatology 2005;153:1200-1203.
  2. Naito K, Morioka S, Nakajima S, Ogawa H. Proteinase inhibitors block formation of pemphigus acantholysis in experiments models of neonatal mice and skin explants: effects of synthetic and plasma proteinase inhibitors on pemphigus acantholysis. J Invest Dermatol 1989; 93: 173-7.

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