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

Kwanghoon Lee, Heun Jung Cho, Hong Suk Kim, Won Jae Lee, Sungnack Lee, Dongsik Bang

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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 NH2 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 α (TNFα) or interleukin-1α (IL-1α) 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 TNFα nor IL-1α 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 μM. 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 TNFα or IL-1α from HDMEC. ERK1/2 are involved in expression of ICAM-1 on HDMEC stimulated with IgM-AECA.

Original languageEnglish
Pages (from-to)63-72
Number of pages10
JournalJournal of Dermatological Science
Volume30
Issue number1
DOIs
Publication statusPublished - 2002 Oct 1

Fingerprint

Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Endothelial cells
Endothelial Cells
Chemical activation
Immunoglobulin M
Skin
Cell Adhesion Molecules
Intercellular Adhesion Molecule-1
Serum
Mitogen-Activated Protein Kinases
Interleukin-1
Assays
Immunosorbents
Tumor Necrosis Factor-alpha
Sorting
Flow Cytometry
anti-endothelial cell antibody
Fluorescence
Enzyme-Linked Immunosorbent Assay

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology

Cite this

@article{410cd9e9c4014017a1edf57691c12014,
title = "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 Beh{\cc}et's disease",
abstract = "Anti-endothelial cell antibodies (AECA) have been detected in the sera of patients with Beh{\cc}et'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 NH2 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 α (TNFα) or interleukin-1α (IL-1α) 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 TNFα nor IL-1α 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 μM. 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 TNFα or IL-1α from HDMEC. ERK1/2 are involved in expression of ICAM-1 on HDMEC stimulated with IgM-AECA.",
author = "Kwanghoon Lee and Cho, {Heun Jung} and Kim, {Hong Suk} and Lee, {Won Jae} and Sungnack Lee and Dongsik Bang",
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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, Kwanghoon; Cho, Heun Jung; Kim, Hong Suk; Lee, Won Jae; Lee, Sungnack; Bang, Dongsik.

In: Journal of Dermatological Science, Vol. 30, No. 1, 01.10.2002, p. 63-72.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 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

AU - Lee, Kwanghoon

AU - Cho, Heun Jung

AU - Kim, Hong Suk

AU - Lee, Won Jae

AU - Lee, Sungnack

AU - Bang, Dongsik

PY - 2002/10/1

Y1 - 2002/10/1

N2 - 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 NH2 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 α (TNFα) or interleukin-1α (IL-1α) 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 TNFα nor IL-1α 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 μM. 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 TNFα or IL-1α from HDMEC. ERK1/2 are involved in expression of ICAM-1 on HDMEC stimulated with IgM-AECA.

AB - 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 NH2 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 α (TNFα) or interleukin-1α (IL-1α) 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 TNFα nor IL-1α 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 μM. 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 TNFα or IL-1α from HDMEC. ERK1/2 are involved in expression of ICAM-1 on HDMEC stimulated with IgM-AECA.

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