TY - JOUR
T1 - Kappa and delta opioid receptors are expressed but down-regulated in fibroblast-like synoviocytes of patients with rheumatoid arthritis and osteoarthritis
AU - Shen, Hua
AU - Aeschlimann, André
AU - Reisch, Nataša
AU - Gay, Renate E.
AU - Simmen, Beat R.
AU - Michel, Beat A.
AU - Gay, Steffen
AU - Sprott, Haiko
PY - 2005/5
Y1 - 2005/5
N2 - Objective. To investigate the expression and regulation of the κ-opioid receptor (KOR) and the δ-opioid receptor (DOR) in fibroblast-like synoviocytes (FLS) from patients with osteoarthritis (OA) and rheumatoid arthritis (RA), and to explore the potential antiarthritic mechanisms of peripheral KORs. Methods. FLS isolated from synovial tissues of 6 OA patients, 8 RA patients, and 2 healthy individuals were exposed to the selective KOR agonist U69593, the selective DOR agonist SNC 80, and κ-opioid dynorphin A in the presence or absence of the KOR antagonist nor-binaltorphimine, the DOR antagonist naltrindole, and the proinflammatory cytokines tumor necrosis factor α (TNFα) and interleukin-1β (IL-1β). The expression of KOR and DOR in OA and RA FLS was evaluated on the messenger RNA (mRNA) and protein levels with TaqMan real-time reverse transcriptase-polymerase chain reaction and immunofluorescence staining, respectively. KOR/DOR-mediated activation of ERK-1 and ERK-2 was investigated by Western blotting. Results. We detected functional KOR and DOR in normal FLS and observed a reduction of both receptors in OA and RA FLS, which was more distinct in RA FLS. U69593 enhanced KOR mRNA expression in both OA and RA FLS in a KOR antagonist-reversible manner. However, the dose required for maximal enhancement in RA FLS was 10 times higher than that required in OA FLS. TNFα and IL-1β both suppressed the expression of DOR and KOR mRNA in both OA and RA FLS. Conclusion. DOR and KOR are constitutively present in normal FLS and are suppressed under inflammatory conditions, such as RA and OA. Most interestingly, the KOR agonist U69593 may exert an antiarthritic effect via up-regulation of KOR in OA and RA FLS.
AB - Objective. To investigate the expression and regulation of the κ-opioid receptor (KOR) and the δ-opioid receptor (DOR) in fibroblast-like synoviocytes (FLS) from patients with osteoarthritis (OA) and rheumatoid arthritis (RA), and to explore the potential antiarthritic mechanisms of peripheral KORs. Methods. FLS isolated from synovial tissues of 6 OA patients, 8 RA patients, and 2 healthy individuals were exposed to the selective KOR agonist U69593, the selective DOR agonist SNC 80, and κ-opioid dynorphin A in the presence or absence of the KOR antagonist nor-binaltorphimine, the DOR antagonist naltrindole, and the proinflammatory cytokines tumor necrosis factor α (TNFα) and interleukin-1β (IL-1β). The expression of KOR and DOR in OA and RA FLS was evaluated on the messenger RNA (mRNA) and protein levels with TaqMan real-time reverse transcriptase-polymerase chain reaction and immunofluorescence staining, respectively. KOR/DOR-mediated activation of ERK-1 and ERK-2 was investigated by Western blotting. Results. We detected functional KOR and DOR in normal FLS and observed a reduction of both receptors in OA and RA FLS, which was more distinct in RA FLS. U69593 enhanced KOR mRNA expression in both OA and RA FLS in a KOR antagonist-reversible manner. However, the dose required for maximal enhancement in RA FLS was 10 times higher than that required in OA FLS. TNFα and IL-1β both suppressed the expression of DOR and KOR mRNA in both OA and RA FLS. Conclusion. DOR and KOR are constitutively present in normal FLS and are suppressed under inflammatory conditions, such as RA and OA. Most interestingly, the KOR agonist U69593 may exert an antiarthritic effect via up-regulation of KOR in OA and RA FLS.
UR - http://www.scopus.com/inward/record.url?scp=18644363291&partnerID=8YFLogxK
U2 - 10.1002/art.21141
DO - 10.1002/art.21141
M3 - Article
C2 - 15880345
AN - SCOPUS:18644363291
SN - 0004-3591
VL - 52
SP - 1402
EP - 1410
JO - Arthritis and rheumatism
JF - Arthritis and rheumatism
IS - 5
ER -