MAPK signaling in psoriasis

Psoriasis is characterized by hyperproliferation of keratinocytes and increased expression of integrins, but the pathological signaling pathway remains unknown. In August 15 Journal of Clinical Investigation, Ingo Haase and colleagues from the Imperial Cancer Research Fund, London, UK show that activation of mitogen-activated protein kinase (MAPK) pathway by integrins, either directly or through increased IL-1 production, is responsible for epidermal hyperproliferation in psoriasis and wound healing.

Haase et al. investigated the activation of MAPK in normal skin, healing wounds and psoriatic lesions from humans and transgenic mice expressing integrins. They found that phenotypically normal epidermis did not contain activated MAP kinase while constitutive activation of MAPK increased the growth rate of keratinocytes and recreated the histological features of psoriasis. In addition, transgene-positive keratinocytes produced more IL-1 than controls, and keratinocyte MAPK could be activated by ligation of suprabasal integrins or treatment with IL-1 (J Clin Invest, 2001,...