Beshay E, Croze F, Prud'homme G J
The Department of Pathology, McGill University, 3775 University Street, Montreal, Quebec, H3A 2B4, Canada.
Clin Immunol. 2001 Feb;98(2):272-9. doi: 10.1006/clim.2000.4964.
We studied the effects of the phosphodiesterase inhibitors pentoxifylline (PTX) and rolipram (ROL) on nitric oxide (NO) production by macrophages and correlated this with cellular cAMP levels. The RAW 264.7 cell line or mouse peritoneal macrophages were activated with lipopolysaccharide (LPS) and interferon gamma (IFN gamma), with or without ROL, PTX, cAMP analogues, or Forskolin. In vivo, peritoneal macrophages were stimulated with staphylococcal enterotoxin B with or without administration of ROL. Nitrite levels in culture and the total cellular cAMP levels were measured. ROL and PTX suppressed NO production of LPS/IFN gamma-stimulated macrophages. ROL (IC(50) = 68-74 microM) was about 40 times more potent than PTX (IC(50) = 2.4-2.9 mM). The suppression paralleled increased total cellular cAMP level (EC(50) = 68-72 microM) and was mimicked by other cAMP elevating agents. ROL and PTX suppressed inducible NO synthase at the mRNA level. The inhibition of NO production of macrophages by ROL or PTX could be beneficial in NO-mediated inflammatory and/or autoimmune disorders.
我们研究了磷酸二酯酶抑制剂己酮可可碱（PTX）和咯利普兰（ROL）对巨噬细胞产生一氧化氮（NO）的影响，并将其与细胞内cAMP水平相关联。用脂多糖（LPS）和干扰素γ（IFNγ）激活RAW 264.7细胞系或小鼠腹腔巨噬细胞，同时添加或不添加ROL、PTX、cAMP类似物或福斯高林。在体内，用葡萄球菌肠毒素B刺激腹腔巨噬细胞，同时给予或不给予ROL。测量培养物中的亚硝酸盐水平和细胞内总cAMP水平。ROL和PTX抑制LPS/IFNγ刺激的巨噬细胞产生NO。ROL（IC50 = 68 - 74 microM）的效力比PTX（IC50 = 2.4 - 2.9 mM）强约40倍。这种抑制作用与细胞内总cAMP水平升高（EC50 = 68 - 72 microM）平行，并且其他cAMP升高剂也能模拟这种作用。ROL和PTX在mRNA水平上抑制诱导型NO合酶。ROL或PTX对巨噬细胞产生NO的抑制作用可能对NO介导的炎症和/或自身免疫性疾病有益。
