Bucillamine mechanism inhibiting IL-1β-induced VEGF production from fibroblast-like synoviocytes

Tsuji, Fumio; Seki, Iwao; Aono, Hiroyuki; Odani, Noriko; Mizutani, Keiko; Okamoto, Masahiro; Sasano, Minoru

doi:10.1016/j.intimp.2007.07.020

Cited by 15 publications

(14 citation statements)

References 34 publications

(30 reference statements)

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“…Moreover, we showed that SA981, an intramolecular disulfide form of bucillamine, inhibits the phosphorylation of Akt [14]. Therefore, Akt is thought to be an essential target of bucillamine.…”

Section: Discussionmentioning

confidence: 87%

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The investigation of synovial genomic targets of bucillamine with microarray technique

et al. 2009

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Bucillamine effectively inhibited fibroblast growth factor (FGF) signaling and tight junction signaling activated by IL-1 beta in FLS. Suppression of these signal pathways may correlate with the pharmacologic mechanisms of bucillamine. In particular, the suppression of FGF signaling by bucillamine is remarkable because the activation of FGF signaling may be involved in rheumatoid arthritis pathology.

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Section: Discussionmentioning

confidence: 87%

“…The results suggest that the effect of SA981 on VEGF production arises partially from inhibition of the phosphorylation of Akt and the expression of transcription factor, hypoxiainducible factor-1b (HIF-1b) and specificity protein 1 (Sp1) by IL-1b [14].…”

Section: Introductionmentioning

confidence: 99%

The investigation of synovial genomic targets of bucillamine with microarray technique

et al. 2009

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“…These properties of Buc and ETN may synergistically act on cytokine production in vivo. Buc also inhibits Akt signaling and vascular endothelial growth factor production [18]. In contrast, ETN inhibits TNF-a and TNF-b.…”

Section: Discussionmentioning

confidence: 99%

“…The antirheumatic effects of Buc may be caused by its modifying effects on the functions of lymphocytes [11][12][13] and synovial cells [14][15][16] as well as by its antioxidant effects [17]. Recent studies have shown that Buc partially inhibits Akt signaling [18,19]. We chose a dose of 30 mg/kg/day for Buc, which does not show significant inhibition of the development of arthritis as a therapeutic treatment.…”

Section: Discussionmentioning

confidence: 99%

Combined effects of bucillamine and etanercept on a rat type II collagen-induced arthritis model

et al. 2010

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The combined effects of bucillamine (Buc) and etanercept (ETN) on a rat model of type II collagen (CII)-induced arthritis (CIA) after treatment onset were investigated. In the combination treatment, rats received Buc 30 mg/kg orally administered once daily from the onset of arthritis or from 4 days after the onset of arthritis and ETN 0.3 mg/kg subcutaneously administered once on the day of onset. The effects of monotherapy with Buc and ETN, respectively, and of Buc + ETN combination therapy on the resulting polyarthritis were evaluated by histopathological analyses and measurements of hindpaw volumes, serum anti-collagen antibody and immunoglobulin levels, and cytokine levels. The Buc + ETN therapeutic combination reduced hindpaw swelling, synovial proliferation, bone destruction, new bone formation, and inflammatory cell infiltration in CIA. Montherapy with Buc showed a tendency to ameliorate these symptoms, while monotherapy with ETN reduced hindpaw swelling at 4 days after administration but did not maintain treatment efficacy toward the end of the experimental period. Histopathological findings did not reveal any efficacy of the ETN therapy. ETN alone increased the serum immunoglobulin levels, while its combination with Buc reduced these levels. Similar results were obtained for serum anti-CII antibody titers. The Buc + ETN combination treatment also reduced serum interleuking (IL)-1alpha and granulocyte macrophage colony-stimulating factor and tended to reduce serum IL-1beta and IL-6 levels. These results suggest that a combination therapy of Buc and ETN may be effective for the treatment of rheumatoid arthritis (RA).

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“…The potentiation of therapeutic effects with the combination of two drugs suggests differences in the site or mechanism of action at or by which these two DMARDs exhibit anti-rheumatoid effects. According to a recent report, bucillamine suppresses IgM production by B cells [7], VEGF production by synoviocytes [8], and differentiation of monocytes into osteoclasts [9] based on a mechanism of action completely different from that of MTX or SSZ. In fact, it has been reported in two large clinical trials in European countries that combined treatment with MTX and SSZ, which have the similar mechanism of action [10,11], dose not provide a clear benefit, when compared with monotherapy using either agent [12,13].…”

Section: Introductionmentioning

confidence: 99%

The efficacy and safety of bucillamine as a second-line DMARD in the treatment of rheumatoid arthritis: a retrospective cohort study

et al. 2008

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We investigated the efficacy and safety of bucillamine administered as a second-line DMARD compared to administration as a first-line DMARD in the treatment of rheumatoid arthritis (RA). We conducted a retrospective cohort study and reviewed medical records of 86 patients with active RA who began to receive bucillamine at Yokohama Minami Kyosai Hospital between January 1998 and July 2004. The efficacy of treatments was compared based on rates of achievement of 20, 50, and 70% improvement in ACR core set 6 months after initiation of the therapy. In the group administered bucillamine as a first-line DMARD (18 patients), 44.4, 22.2, and 11.1% of patients achieved ACR 20, 50, 70, respectively, while 56.5, 34.1, and 19.5% achieved ACR 20, 50, 70, respectively, in the group administered bucillamine following switching from MTX (46 patients), and 53.3, 33.3, and 13.3% achieved ACR 20, 50, and 70, respectively, in the group administered bucillamine following switching from Sulfasalazine (SSZ) (15 patients). The rates of achievements of ACR 20, 50, 70 did not differ statistically between the three groups and there was no increase in risk of serious adverse effects related to previous DMARDs. The usefulness of bucillamine as a second-line DMARD was demonstrated.

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Bucillamine mechanism inhibiting IL-1β-induced VEGF production from fibroblast-like synoviocytes

Cited by 15 publications

References 34 publications

The investigation of synovial genomic targets of bucillamine with microarray technique

The investigation of synovial genomic targets of bucillamine with microarray technique

Combined effects of bucillamine and etanercept on a rat type II collagen-induced arthritis model

The efficacy and safety of bucillamine as a second-line DMARD in the treatment of rheumatoid arthritis: a retrospective cohort study

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