Expression and localization of the activated mitogen-activated protein kinase in lesional psoriatic skin.
Abnormalities in several signaling pathways and in the expression and/or activation of different transcription factors in psoriatic keratinocytes have been hypothesized to play a role in the pathophysiology of psoriasis. The mitogen-activated protein kinase (MAPK) cascades are among the best characterized of intracellular signaling pathways, and they play important roles in cell proliferation, differentiation, gene expression, and inflammation. We investigated the expression, activation and distribution of extracellular signal-regulated kinases (ERKs), p38 mitogen-activated protein kinases (p38 MAPK) and c-Jun N-terminal kinases (JNKs), using immunohistochemistry and Western blot in lesional psoriatic skin and normal control skin, to clarify the possible roles of these kinases involved in the pathogenesis of psoriasis. The immunoblot analysis demonstrated that activation of ERK1/2 and p38 MAPK increased in the lesional psoriatic skin. In addition, a significant increase in p-MEK (the upstream activator of ERK), and p-CREB (a downstream transcription factor of active ERK) was also found in our experiment. The immunohistochemical study showed that the levels of phosphorylated ERK1/2 and p38 MAPK were enhanced in lesional psoriatic skin compared with controls. Phosphorylated ERK1/2 and p38 exhibited clear nuclear localization throughout the epidermal part of lesional psoriatic skin. These findings suggested that ERK1/2 and p38 pathways were involved in the pathophysiology of psoriasis.
Yu
Xiao-Jing
XJ
Department of Dermatology, Qilu Hospital, University of Shandong, Jinan 250012, China.
Li
Chun-Yang
CY
Dai
Hong-Yan
HY
Cai
Da-Xing
DX
Wang
Ke-Yu
KY
Xu
Yong-Hao
YH
Chen
La-Mei
LM
Zhou
Chun-Lei
CL
D000328:Adult; D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000502:physiology*; D011565:Psoriasis / Q000378:metabolism / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases