Please use this identifier to cite or link to this item: https://doi.org/10.1155/2007/58901
Title: Administration of PDE4 inhibitors suppressed the pannus-like inflammation by inhibition of cytokine production by macrophages and synovial fibroblast proliferation
Authors: Kobayashi, K
Suda, T 
Manabe, H
Miki, I
Keywords: bovine serum albumin
cilomilast
diclofenac
hydroxyproline
interleukin 12
interleukin 1beta
kf 66490
leflunomide
lipopolysaccharide
methotrexate
myeloperoxidase
phosphodiesterase IV inhibitor
prednisolone
thioglycolic acid
tumor necrosis factor alpha
unclassified drug
cytokine
phosphodiesterase IV
animal experiment
animal model
animal tissue
article
cell proliferation
controlled study
cytokine production
drug mechanism
enzyme activity
granuloma
inflammation
macrophage
male
mouse
nonhuman
priority journal
rheumatoid arthritis
animal
Bagg albino mouse
drug antagonism
fibroblast
inflammation
macrophage
metabolism
oral drug administration
subcutaneous drug administration
synovium
Animalia
Bovinae
Murinae
Mus
Rattus
Administration, Oral
Animals
Arthritis, Rheumatoid
Cell Proliferation
Cyclic Nucleotide Phosphodiesterases, Type 4
Cytokines
Fibroblasts
Inflammation
Injections, Subcutaneous
Macrophages
Male
Mice
Mice, Inbred BALB C
Serum Albumin, Bovine
Synovial Membrane
Issue Date: 2007
Citation: Kobayashi, K, Suda, T, Manabe, H, Miki, I (2007). Administration of PDE4 inhibitors suppressed the pannus-like inflammation by inhibition of cytokine production by macrophages and synovial fibroblast proliferation. Mediators of Inflammation 2007 : 58901. ScholarBank@NUS Repository. https://doi.org/10.1155/2007/58901
Rights: Attribution 4.0 International
Abstract: A marked proliferation of synovial fibroblasts in joints leads to pannus formation in rheumatoid arthritis (RA). Various kinds of cytokines are produced in the pannus. The purpose of this study is to elucidate the effects of phosphodiesterase 4 (PDE4) inhibitors in a new animal model for the evaluation of pannus formation and cytokine production in the pannus. Mice sensitized with methylated bovine serum albumin (mBSA) were challenged by subcutaneous implantation of a membrane filter soaked in mBSA solution in the back of the mice. Drugs were orally administered for 10 days. The granuloma formed around the filter was collected on day 11. It was chopped into pieces and cultured in vitro for 24 hr. The cytokines were measured in the supernatants. The type of cytokines produced in the granuloma was quite similar to those produced in pannus in RA. Both PDE4 inhibitors, KF66490 and SB207499, suppressed the production of IL-1?, TNF-?, and IL-12, and the increase in myeloperoxidase activity, a marker enzyme for neutrophils and hydroxyproline content. Compared to leflunomide, PDE4 inhibitors more strongly suppressed IL-12 production and the increase in myeloperoxidase activity. PDE4 inhibitors also inhibited lipopolysaccharide-induced TNF-? and IL-12 production from thioglycolate-induced murine peritoneal macrophages and the proliferation of rat synovial fibroblasts. These results indicate this model makes it easy to evaluate the effect of drugs on various cytokine productions in a granuloma without any purification step and may be a relevant model for evaluating novel antirheumatic drugs on pannus formation in RA. PDE4 inhibitors could have therapeutic effects on pannus formation in RA by inhibition of cytokine production by macrophages and synovial fibroblast proliferation. Copyright © 2007 Katsuya Kobayashi et al.
Source Title: Mediators of Inflammation
URI: https://scholarbank.nus.edu.sg/handle/10635/181029
ISSN: 0962-9351
DOI: 10.1155/2007/58901
Rights: Attribution 4.0 International
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