Nifedipine protects against overproduction of superoxide anion by monocytes from patients with systemic sclerosis

Arthritis Research & Therapy

Yannick Allanore³  Didier Borderie²  Axel Périanin¹  Hervé Lemaréchal²  Ohvanesse Garabed Ekindjian²  André Kahan³ 

[1] Cell Biology Department, Cochin Institute, CNRS UMR 8104, INSERM 0567, Paris, France

[2] Biochemistry A Department, Paris V University, Assistance Publique-Hôpitaux de Paris, Cochin Hospital, Paris, France

[3] Rheumatology A Department, Paris V University, Assistance Publique-Hôpitaux de Paris, Cochin Hospital, Paris, France

关键词: systemic sclerosis;    superoxide anion;    protein kinase C;    nifedipine;    monocyte;   

Others  :  1101168
DOI  :  10.1186/ar1457

 received in 2004-06-05, accepted in 2004-10-08,  发布年份 2004

【 摘 要 】

We have reported previously that dihydropyridine-type calcium-channel antagonists (DTCCA) such as nifedipine decrease plasma markers of oxidative stress damage in systemic sclerosis (SSc). To clarify the cellular basis of these beneficial effects, we investigated the effects in vivo and in vitro of nifedipine on superoxide anion (O₂^•-) production by peripheral blood monocytes. We compared 10 healthy controls with 12 patients with SSc, first after interruption of treatment with DTCCA and second after 2 weeks of treatment with nifedipine (60 mg/day). O₂^•- production by monocytes stimulated with phorbol myristate acetate (PMA) was quantified by the cytochrome c reduction method. We also investigated the effects in vitro of DTCCA on O₂^•- production and protein phosphorylation in healthy monocytes and on protein kinase C (PKC) activity using recombinant PKC. After DTCCA had been washed out, monocytes from patients with SSc produced more O₂^•- than those from controls. Nifedipine treatment considerably decreased O₂^•- production by PMA-stimulated monocytes. Treatment of healthy monocytes with nifedipine in vitro inhibited PMA-induced O₂^•- production and protein phosphorylation in a dose-dependent manner. Finally, nifedipine strongly inhibited the activity of recombinant PKC in vitro. Thus, the oxidative stress damage observed in SSc is consistent with O₂^•- overproduction by primed monocytes. This was decreased by nifedipine treatment both in vivo and in vitro. This beneficial property of nifedipine seems to be mediated by its cellular action and by the inhibition of PKC activity. This supports the hypothesis that this drug could be useful for the treatment of diseases associated with oxidative stress.

【 授权许可】

   
2004 Allanore et al.; licensee BioMed Central Ltd.

【 图 表 】

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