CYP7B Expression and Activity in Fibroblast-Like Synoviocytes From Patients With Rheumatoid Arthritis Regulation by Proinflammatory Cytokines

John Dulos; Monique A. J. van der Vleuten; Annemieke Kavelaars; Cobi J. Heijnen; Annemieke M. Boots

doi:10.1002/art.20950

CYP7B Expression and Activity in Fibroblast-Like Synoviocytes From Patients With Rheumatoid Arthritis Regulation by Proinflammatory Cytokines

John Dulos^*, Monique A. J. van der Vleuten, Annemieke Kavelaars, Cobi J. Heijnen, Annemieke M. Boots

^*Corresponding author for this work

Translational Immunology Groningen (TRIGR)

Research output: Contribution to journal › Article › Academic › peer-review

48 Citations (Scopus)

Abstract

Objective. The cytochrome P450 enzyme CYP7B catalyzes the conversion of dehydroepiandrosterone (DHEA) into 7 alpha-hydroxy-DHEA (7 alpha-OH-DHEA). This metabolite can stimulate the immune response. We previously reported that the severity of murine collagen-induced arthritis is correlated with CYP7B messenger RNA (mRNA) expression and activity in the arthritic joint. The purpose of this study was to investigate the presence of 7 alpha-OH-DHEA in synovial samples and the cytokine regulation of CYP7B activity in fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA).

Methods. The presence of 7 alpha-OH-DHEA was examined in synovial biopsy tissues, synovial fluid, and serum by radioimmunoassay. The effect of cytokines on CYP7B mRNA expression and CYP7B activity in FLS was examined by determining the formation of the CYP7B enzyme product 7 alpha-OH-DHEA with the use of high-performance liquid chromatography.

Results. The CYP7B enzyme product 7 alpha-OH-DHEA was found in synovial biopsy tissues, synovial fluid, and serum from RA patients. The proinflammatory cytokines tumor necrosis factor alpha (TNF alpha), interleukin-1 alpha (IL-1 alpha), IL-1 beta, and IL-17 up-regulated CYP7B activity in an FLS cell line 2-10-fold. Enhanced CYP7B activity was correlated with an increase in CYP7B mRNA. The cytokine transforming growth factor beta inhibited CYP7 beta activity. Moreover, CYP7B activity was detected in 10 of 13 unstimulated synovial fibroblast cell lines. Stimulation with TNF alpha increased CYP7 beta activity in all cell lines tested.

Conclusion. Exposure to the proinflammatory cytokines TNF alpha, IL-1 alpha, IL-1,6, and IL-17 increases CVP7B activity in synovial tissue. Increased CYP7B activity leads to higher levels of the DHEA metabolite 7 alpha-OH-DHEA in synovial fluid, which may contribute to the maintenance of the chronic inflammation observed in RA patients.

Original language	English
Pages (from-to)	770-778
Number of pages	9
Journal	ARTHRITIS AND RHEUMATISM
Volume	52
Issue number	3
DOIs	https://doi.org/10.1002/art.20950
Publication status	Published - Mar-2005

Keywords

NECROSIS-FACTOR-ALPHA
DEHYDROEPIANDROSTERONE DHEA
IMMUNE-RESPONSE
SYNOVIAL FIBROBLASTS
DOWN-REGULATION
MESSENGER-RNA
TNF-ALPHA
T-CELLS
RECEPTOR
MICE

Access to Document

10.1002/art.20950

Handle.net

Persistent link

Cite this

@article{52aee1d1d27a444595151cab6f678472,

title = "CYP7B Expression and Activity in Fibroblast-Like Synoviocytes From Patients With Rheumatoid Arthritis Regulation by Proinflammatory Cytokines",

abstract = "Objective. The cytochrome P450 enzyme CYP7B catalyzes the conversion of dehydroepiandrosterone (DHEA) into 7 alpha-hydroxy-DHEA (7 alpha-OH-DHEA). This metabolite can stimulate the immune response. We previously reported that the severity of murine collagen-induced arthritis is correlated with CYP7B messenger RNA (mRNA) expression and activity in the arthritic joint. The purpose of this study was to investigate the presence of 7 alpha-OH-DHEA in synovial samples and the cytokine regulation of CYP7B activity in fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA).Methods. The presence of 7 alpha-OH-DHEA was examined in synovial biopsy tissues, synovial fluid, and serum by radioimmunoassay. The effect of cytokines on CYP7B mRNA expression and CYP7B activity in FLS was examined by determining the formation of the CYP7B enzyme product 7 alpha-OH-DHEA with the use of high-performance liquid chromatography.Results. The CYP7B enzyme product 7 alpha-OH-DHEA was found in synovial biopsy tissues, synovial fluid, and serum from RA patients. The proinflammatory cytokines tumor necrosis factor alpha (TNF alpha), interleukin-1 alpha (IL-1 alpha), IL-1 beta, and IL-17 up-regulated CYP7B activity in an FLS cell line 2-10-fold. Enhanced CYP7B activity was correlated with an increase in CYP7B mRNA. The cytokine transforming growth factor beta inhibited CYP7 beta activity. Moreover, CYP7B activity was detected in 10 of 13 unstimulated synovial fibroblast cell lines. Stimulation with TNF alpha increased CYP7 beta activity in all cell lines tested.Conclusion. Exposure to the proinflammatory cytokines TNF alpha, IL-1 alpha, IL-1,6, and IL-17 increases CVP7B activity in synovial tissue. Increased CYP7B activity leads to higher levels of the DHEA metabolite 7 alpha-OH-DHEA in synovial fluid, which may contribute to the maintenance of the chronic inflammation observed in RA patients.",

keywords = "NECROSIS-FACTOR-ALPHA, DEHYDROEPIANDROSTERONE DHEA, IMMUNE-RESPONSE, SYNOVIAL FIBROBLASTS, DOWN-REGULATION, MESSENGER-RNA, TNF-ALPHA, T-CELLS, RECEPTOR, MICE",

author = "John Dulos and {van der Vleuten}, {Monique A. J.} and Annemieke Kavelaars and Heijnen, {Cobi J.} and Boots, {Annemieke M.}",

year = "2005",

month = mar,

doi = "10.1002/art.20950",

language = "English",

volume = "52",

pages = "770--778",

journal = "ARTHRITIS AND RHEUMATISM",

issn = "0004-3591",

publisher = "John Wiley and Sons Inc.",

number = "3",

}

TY - JOUR

T1 - CYP7B Expression and Activity in Fibroblast-Like Synoviocytes From Patients With Rheumatoid Arthritis Regulation by Proinflammatory Cytokines

AU - Dulos, John

AU - van der Vleuten, Monique A. J.

AU - Kavelaars, Annemieke

AU - Heijnen, Cobi J.

AU - Boots, Annemieke M.

PY - 2005/3

Y1 - 2005/3

N2 - Objective. The cytochrome P450 enzyme CYP7B catalyzes the conversion of dehydroepiandrosterone (DHEA) into 7 alpha-hydroxy-DHEA (7 alpha-OH-DHEA). This metabolite can stimulate the immune response. We previously reported that the severity of murine collagen-induced arthritis is correlated with CYP7B messenger RNA (mRNA) expression and activity in the arthritic joint. The purpose of this study was to investigate the presence of 7 alpha-OH-DHEA in synovial samples and the cytokine regulation of CYP7B activity in fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA).Methods. The presence of 7 alpha-OH-DHEA was examined in synovial biopsy tissues, synovial fluid, and serum by radioimmunoassay. The effect of cytokines on CYP7B mRNA expression and CYP7B activity in FLS was examined by determining the formation of the CYP7B enzyme product 7 alpha-OH-DHEA with the use of high-performance liquid chromatography.Results. The CYP7B enzyme product 7 alpha-OH-DHEA was found in synovial biopsy tissues, synovial fluid, and serum from RA patients. The proinflammatory cytokines tumor necrosis factor alpha (TNF alpha), interleukin-1 alpha (IL-1 alpha), IL-1 beta, and IL-17 up-regulated CYP7B activity in an FLS cell line 2-10-fold. Enhanced CYP7B activity was correlated with an increase in CYP7B mRNA. The cytokine transforming growth factor beta inhibited CYP7 beta activity. Moreover, CYP7B activity was detected in 10 of 13 unstimulated synovial fibroblast cell lines. Stimulation with TNF alpha increased CYP7 beta activity in all cell lines tested.Conclusion. Exposure to the proinflammatory cytokines TNF alpha, IL-1 alpha, IL-1,6, and IL-17 increases CVP7B activity in synovial tissue. Increased CYP7B activity leads to higher levels of the DHEA metabolite 7 alpha-OH-DHEA in synovial fluid, which may contribute to the maintenance of the chronic inflammation observed in RA patients.

AB - Objective. The cytochrome P450 enzyme CYP7B catalyzes the conversion of dehydroepiandrosterone (DHEA) into 7 alpha-hydroxy-DHEA (7 alpha-OH-DHEA). This metabolite can stimulate the immune response. We previously reported that the severity of murine collagen-induced arthritis is correlated with CYP7B messenger RNA (mRNA) expression and activity in the arthritic joint. The purpose of this study was to investigate the presence of 7 alpha-OH-DHEA in synovial samples and the cytokine regulation of CYP7B activity in fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA).Methods. The presence of 7 alpha-OH-DHEA was examined in synovial biopsy tissues, synovial fluid, and serum by radioimmunoassay. The effect of cytokines on CYP7B mRNA expression and CYP7B activity in FLS was examined by determining the formation of the CYP7B enzyme product 7 alpha-OH-DHEA with the use of high-performance liquid chromatography.Results. The CYP7B enzyme product 7 alpha-OH-DHEA was found in synovial biopsy tissues, synovial fluid, and serum from RA patients. The proinflammatory cytokines tumor necrosis factor alpha (TNF alpha), interleukin-1 alpha (IL-1 alpha), IL-1 beta, and IL-17 up-regulated CYP7B activity in an FLS cell line 2-10-fold. Enhanced CYP7B activity was correlated with an increase in CYP7B mRNA. The cytokine transforming growth factor beta inhibited CYP7 beta activity. Moreover, CYP7B activity was detected in 10 of 13 unstimulated synovial fibroblast cell lines. Stimulation with TNF alpha increased CYP7 beta activity in all cell lines tested.Conclusion. Exposure to the proinflammatory cytokines TNF alpha, IL-1 alpha, IL-1,6, and IL-17 increases CVP7B activity in synovial tissue. Increased CYP7B activity leads to higher levels of the DHEA metabolite 7 alpha-OH-DHEA in synovial fluid, which may contribute to the maintenance of the chronic inflammation observed in RA patients.

KW - NECROSIS-FACTOR-ALPHA

KW - DEHYDROEPIANDROSTERONE DHEA

KW - IMMUNE-RESPONSE

KW - SYNOVIAL FIBROBLASTS

KW - DOWN-REGULATION

KW - MESSENGER-RNA

KW - TNF-ALPHA

KW - T-CELLS

KW - RECEPTOR

KW - MICE

U2 - 10.1002/art.20950

DO - 10.1002/art.20950

M3 - Article

SN - 0004-3591

VL - 52

SP - 770

EP - 778

JO - ARTHRITIS AND RHEUMATISM

JF - ARTHRITIS AND RHEUMATISM

IS - 3

ER -

CYP7B Expression and Activity in Fibroblast-Like Synoviocytes From Patients With Rheumatoid Arthritis Regulation by Proinflammatory Cytokines

Abstract

Keywords

Access to Document

Handle.net

Fingerprint

Cite this