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The mitogen‐activated protein kinases p38 and ERK1/2 are increased in lesional psoriatic skin
Author(s) -
Johansen C.,
Kragballe K.,
Westergaard M.,
Henningsen J.,
Kristiansen K.,
Iversen L.
Publication year - 2005
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/j.1365-2133.2004.06304.x
Subject(s) - psoriasis , p38 mitogen activated protein kinases , kinase , mapk/erk pathway , mitogen activated protein kinase , protein kinase a , medicine , cancer research , biology , immunology , microbiology and biotechnology
Summary Background Alterations in specific signal transduction pathways may explain the hyperproliferation and abnormal differentiation of the keratinocytes as well as the increased expression of inflammatory cytokines seen in psoriasis. Major signalling pathways used by eukaryotic cells to transduce extracellular signals into cellular responses impinge on the mitogen‐activated protein kinases (MAPKs). Objectives To investigate the expression of the MAPK p38, extracellular signal‐regulated kinase (ERK) and c‐Jun NH 2 ‐terminal kinase (JNK) in psoriatic skin. Methods Keratome biopsies were taken from patients with plaque‐type psoriasis. Western blot analysis was used to determine p38, ERK and JNK activity and protein levels, whereas kinase assays were used to examine the kinase activity of p38. Results We demonstrated increased levels of the phosphorylated forms of p38 and ERK1/2 in lesional psoriatic skin compared with nonlesional psoriatic skin. No abnormality was found in the activation and expression of JNK1/2. Ex vivo kinase assays confirmed the increased activation of p38, and furthermore demonstrated increased kinase activity of the p38 isoforms p38α, p38β and p38δ in lesional compared with nonlesional psoriatic skin. p38γ was not detected in the psoriatic skin. Clearance of the psoriatic lesions, induced by climatotherapy at the Dead Sea for 4 weeks, led to a normalization in the activity of both p38 and ERK1/2. Conclusions Taken together, our results demonstrate that the activity of the MAPKs p38α, p38β and p38δ and ERK1/2 are increased in lesional psoriatic skin compared with nonlesional psoriatic skin, and that clearance of psoriasis normalizes the p38 and ERK1/2 activity. Thus, p38 and ERK1/2 might be potential targets in the treatment of psoriasis.