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Activation of extracellular signal regulated kinase 1/2 in human dermal microvascular endothelial cells stimulated by anti-endothelial cell antibodies in sera of patients with Behçet's disease.

Lee, KH; Cho, HJ; Kim, HS; Lee, WJ; Lee, S; Bang, D
Journal of dermatological science, 30(1):63-72, 2002
Journal Title
Journal of dermatological science
Anti-endothelial cell antibodies (AECA) have been detected in the sera of patients with Behçet's disease (BD). The isotype of AECA from BD is IgM recognizing 44 kDa antigen (IgM-AECA) of human dermal microvascular endothelial cells (HDMEC). After stimulation of HDMEC with AECA-positive sera from BD patients, the expression of intercellular cell adhesion molecule-1 (ICAM-1) on HDMEC increases significantly. Mitogen-activated protein kinase (MAPK) cascade is one of protein kinase families activated by a wide spectrum of extracellular stimuli. There are several subtypes, including extracellular signal regulated kinase (ERK)1/2, c-Jun NH(2) terminal kinase (JNK), and p38 cascades, and they regulate various cellular processes such as cell growth, differentiation, and inflammation. We examined the involvement of MAPK as a signal transduction pathway in the IgM-AECA-induced ICAM-1 expression. We used enzyme-linked immunosorbent assay (ELISA) and fluorescence-activated cell sorting (FACS) for detecting the induction of ICAM-1 on HDMEC. We also examined the production of tumor necrosis factor alpha (TNFalpha) or interleukin-1alpha (IL-1alpha) by HDMEC after stimulation with IgM-AECA, and checked the involvement of MAPK by Western blot assay. IgM-AECA cocktail from 8 patients with BD induced expression of the ICAM-1 on HDMEC. Neither TNFalpha nor IL-1alpha was detected by ELISA, FACS or reverse transcriptase-polymerase chain reaction in activated HDMEC cultures. IgM-AECA cocktail activated ERK1/2 and showed peak activities at 5 min after the stimulation. Specific MAPK/ERK kinase inhibitor PD98059 inhibited IgM-AECA-induced ERK1/2 activities and ICAM-1 expression on HDMEC at a concentration of 60 microM. IgM-AECA can play a pathogenic role in induction of vasculitis and inflammatory lesions of BD by directly activating endothelial cells, not by production of TNFalpha or IL-1alpha from HDMEC. ERK1/2 are involved in expression of ICAM-1 on HDMEC stimulated with IgM-AECA.
MeSH terms
Autoantibodies/pharmacologyBehcet Syndrome/blood/*enzymology/geneticsEndothelium, Vascular/*enzymologyEnzyme ActivationGene Expression Regulation/immunologyHumansIntercellular Adhesion Molecule-1/geneticsInterleukin-1/geneticsMicrocirculation/physiologyMitogen-Activated Protein Kinase 1/*metabolismMitogen-Activated Protein Kinase 3Mitogen-Activated Protein Kinases/*metabolismRNA, Messenger/geneticsReference ValuesSkin/*blood supplyTumor Necrosis Factor-alpha/genetics
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Journal Papers > School of Medicine / Graduate School of Medicine > Dermatology
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