Tsuji F, Matsuoka H, Aono H, Takai M, Horiuchi M, Nishimura K, Mita S
Discovery Research Division, Santen Pharmaceutical Co., Ltd., Osaka, Japan.
Biol Pharm Bull. 2000 May;23(5):663-5. doi: 10.1248/bpb.23.663.
We investigated the effects of various sulfhydryl compounds on interleukin-1 (IL-1)-induced vascular endothelial growth factor (VEGF) production in human synovial stromal cells (HSSC). HSSC stimulated by IL-1beta (100 ng/ml) produced VEGF and interleukin-6 (IL-6) in vitro. Monosulfhydryl compounds, N-acetylcysteine, D-penicillamine, tiopronin and the bucillamine-like disulfhydryl compound, compound A scarcely affected VEGF or IL-6 production at concentrations of 10(-5) and 10(-4) M. However, the disulfhydryl compound, bucillamine inhibited VEGF production but not IL-6 production at concentrations of 10(-5) and 10(-4) M. These results suggest that bucillamine may be a selective inhibitor of IL-1-induced VEGF production in HSSC, and that inhibition of VEGF production may require not only SH groups but also a specific chemical structure.
我们研究了各种巯基化合物对白细胞介素 -1(IL-1)诱导的人滑膜基质细胞(HSSC)中血管内皮生长因子(VEGF)产生的影响。在体外,受IL-1β(100 ng/ml)刺激的HSSC会产生VEGF和白细胞介素 -6(IL-6)。单巯基化合物N-乙酰半胱氨酸、青霉胺、硫普罗宁以及类布西拉明二巯基化合物A在10^(-5)和10^(-4) M浓度下几乎不影响VEGF或IL-6的产生。然而,二巯基化合物布西拉明在10^(-5)和10^(-4) M浓度下抑制VEGF的产生,但不抑制IL-6的产生。这些结果表明,布西拉明可能是HSSC中IL-1诱导的VEGF产生的选择性抑制剂,并且抑制VEGF的产生可能不仅需要巯基基团,还需要特定的化学结构。