The role of p38 MAPK in the aetiopathogenesis of psoriasis and psoriatic arthritis.

Athanasios Mavropoulos,Dimitrios P Bogdanos,Lazaros I Sakkas,Christos Liaskos,Eirini I Rigopoulou

doi:10.1155/2013/569751

Abstract

The pathogenetic mechanisms responsible for the induction of immune-mediated disorders, such as psoriasis, remain not well characterized. Molecular signaling pathways are not well described in psoriasis, as well as psoriatic arthritis, which is seen in up to 40% of patients with psoriasis. Signaling pathway defects have long been hypothesized to participate in the pathology of psoriasis, yet their implication in the altered psoriatic gene expression still remains unclear. Emerging data suggest a potential pathogenic role for mitogen activated protein kinases p38 (p38 MAPK) extracellular signal-regulated kinase 1/2 (ERK1/2), and c-Jun N-terminal kinase (JNK) in the development of psoriasis. The data are still limited, though, for psoriatic arthritis. This review discusses the current data suggesting a crucial role for p38 MAPK in the pathogenesis of these disorders.

Highlights

Psoriasis is a chronic inflammatory skin disease affecting 1-2% of the population
The Mitogen-activated protein kinase NK (MAPK) kinases constitute an important set of three signaling pathways, namely, p38, extracellular signal-regulated kinase 1/2 (ERK1/2), and Jun N-terminal kinase (JNK), which control several important functions within the cell, such as cell proliferation, differentiation, gene expression, and apoptosis [60]
(5) Dual-specificity phosphatase 1 (DUSP1) is an important negative regulator of p38 MAPK activity DUSP1 mRNA expression is downregulated in psoriatic skin lesions compared with paired samples of nonlesional psoriatic skin

Summary

Introduction

Psoriasis is a chronic inflammatory skin disease affecting 1-2% of the population. Clinically, skin lesions are characterized by erythematous plaques covered by scales and pathologically by keratinocyte hyperproliferation and altered differentiation, inflammatory infiltrates, and neovascularization [1,2,3,4]. These experiments identified mitogen-activated protein kinases p38 (p38 MAPKs), extracellular signal-regulated kinase 1/2 (ERK1/2), and c-Jun N-terminal kinase (JNK) to be involved in the pathogenesis of psoriasis [20,21,22, 58, 59] (Table 2). The MAPK kinases constitute an important set of three signaling pathways, namely, p38, ERK1/2, and JNK, which control several important functions within the cell, such as cell proliferation, differentiation, gene expression, and apoptosis [60].

Results

Conclusion