The role of cyclic-3',5'-adenosine monophosphate in prostaglandin-mediated inhibition of basic calcium phosphate crystal-induced mitogenesis and collagenase induction in cultured human fibroblasts.
The role of cyclic-3',5'-adenosine monophosphate in prostaglandin-mediated inhibition of basic calcium phosphate crystal-induced mitogenesis and collagenase induction in cultured human fibroblasts.
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环-3,5-腺苷单磷酸在前列腺素介导的抑制碱性磷酸钙晶体诱导的有丝分裂和胶原酶诱导的培养人成纤维细胞中的作用。
DOI：
10.1016/0925-4439(94)90064-7
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Cheung,HS
中科院分区：
文献类型：
--
作者：
McCarthy,GM;Cheung,HS
滑液碱性磷酸钙（BCP）晶体与严重破坏性关节病相关，其特征为滑膜增生和关节内胶原结构的非炎性降解。BCP晶体刺激成纤维细胞和软骨细胞有丝分裂，金属蛋白酶分泌和前列腺素的产生。作为一种组织保护作用的前列腺素已被提出，我们最近研究了前列腺素E1对BCP晶体诱导的有丝分裂和胶原酶mRNA积累的人成纤维细胞（HF）的影响。我们证明了BCP晶体诱导的有丝分裂和胶原酶mRNA积累的剂量依赖性抑制。因此，PGE 1抑制BCP晶体诱导的有丝分裂和胶原酶mRNA积累的机制进行了探讨。PGE 1（100 ng/ml）使HF细胞内cAMP增加40倍于对照。BCP单独没有引起这样的变化，但抑制PGE 1诱导的细胞内cAMP增加至少60%。腺苷酸环化酶抑制剂2′，5 ′-二脱氧腺苷（ddA）（10 μM）也能阻断PGE 1诱导的胞内cAMP增加，ddA可逆转PGE 1对BCP晶体诱导的有丝分裂的抑制作用。二丁酸环磷酸腺苷还以浓度依赖性方式抑制BCP晶体诱导的有丝分裂。增加细胞内cAMP水平的药物，如腺苷酸环化酶激活剂毛喉素和磷酸二酯酶抑制剂3-异丁基-1-甲基黄嘌呤（IBMX）模拟了PGE 1对HF胶原酶mRNA水平的影响。PGE 1通过cAMP信号转导途径抑制BCP晶体的生物学效应，这种抑制可能具有重要的治疗意义。
Synovial fluid basic calcium phosphate (BCP) crystals are associated with severe destructive arthropathies characterised by synovial proliferation and non-inflammatory degradation of intra-articular collagenous structures. BCP crystals stimulate fibroblast and chondrocyte mitogenesis, metalloprotease secretion and prostaglandin production. As a tissue protective effect of prostaglandins has been suggested, we recently studied the effect of PGE1on BCP crystal-induced mitogenesis and collagenase mRNA accumulation in human fibroblasts (HF). We demonstrated a dose-dependent inhibition of BCP crystal-induced mitogenesis and collagenase mRNA accumulation. The mechanism of PGE1inhibition of BCP crystal-induced mitogenesis and collagenase mRNA accumulation was therefore explored. PGE1(100 ng/ml) increased HF intracellular cAMP 40-fold over control. BCP alone caused no such change but inhibited the PGE1-induced increase in intracellular cAMP by at least 60%. The PGE1-induced increase in intracellular cAMP was also blocked by the adenyl cyclase inhibitor, 2′,5′-dideoxyadenosine (ddA) (10 μM) and ddA reversed the PGE1-mediated inhibition of BCP crystal-induced mitogenesis. Dibutyrul cAMP also inhibited BCP crystal-induced mitogenesis in a concentration-dependent manner. Agents which increase intracellular cAMP levels such as the adenyl cyclase activator forskolin and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) mimicked the effect of PGE1on HF collagenase mRNA levels. PGE1inhibits the biologic effects of BCP crystals through the cAMP signal transduction pathway and such inhibition may have significant therapeutic implications.
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前列腺素 E1 抑制兔滑膜细胞和人成纤维细胞中胶原酶基因的表达。
影响因子：
4.8
作者：
Salvatori,R;GuidonJr,PT;Rapuano,BE;Bockman,RS
通讯作者：
Bockman,RS
影响因子：
--
作者：
MITCHELL, PG;STRUVE, JA;CHEUNG, HS
通讯作者：
CHEUNG, HS
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DOI：
--
发表时间：
--
期刊：
影响因子：
--
作者：
通讯作者：
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肾上腺素和前列腺素 E-1 对 WI-38 成纤维细胞中环腺苷 3:5-单磷酸水平的影响。
影响因子：
4.8
作者：
L. A. Kelly;R. Butcher
通讯作者：
R. Butcher
培养哺乳动物细胞的腺苷酸环化酶：儿茶酚胺的激活
影响因子：
56.9
作者：
M. Makman
通讯作者：
M. Makman