Lubberts E, Joosten L A, van de Loo F A, van den Gersselaar L A, van den Berg W B
Department of Rheumatology, University Hospital Nijmegen, The Netherlands.
Arthritis Rheum. 2000 Jun;43(6):1300-6. doi: 10.1002/1529-0131(200006)43:6<1300::AID-ANR12>3.0.CO;2-D.
To investigate the role of interleukin-4 (IL-4) and IL-10 in basal and IL-1- and IL-17-mediated inhibition of chondrocyte metabolism.
Cartilage explants of patellae from naive mice were incubated with IL-17 and/or IL-1 alone or were pretreated with IL-4 and IL-10. In addition, knee joints of naive mice were injected intraarticularly with IL-4 and IL-10 alone or were coinjected with IL-1. Chondrocyte proteoglycan (PG) synthesis was measured in intact murine articular cartilage. Levels of nitric oxide (NO) were measured using the Griess reagent.
IL-17, a novel cytokine secreted by CD4+ activated memory T cells, inhibited chondrocyte PG synthesis in intact murine articular cartilage, although the suppressive effect was less potent than that of IL-1. The suppressive effect of IL-17 was completely abolished in the presence of L-NIO (L-NS-[1-iminoethyl]ornithine), an inhibitor of NO metabolism, and IL-17 only slightly induced inhibition of PG synthesis in cartilage explants of patellae from iNOS (inducible NO synthase) knockout mice. This indicates that the suppressive effect of IL-17 was mediated by NO. Pretreatment with IL-4, but not IL-10, significantly reduced the inhibition of chondrocyte PG synthesis induced by IL-1 or IL-17. The IL-4-induced reduction in the inhibitory effects of IL-1 and IL-17 on chondrocyte PG synthesis was accompanied by decreased NO formation in the culture supernatants.
IL-17 plays a role in the inhibition of chondrocyte PG synthesis. IL-4 and IL-10 have no effect on basal chondrocyte metabolism. However, IL-4-pretreated cartilage is less sensitive to the suppressive effect of IL-1 as well as IL-17. This suggests that IL-4 is protective in T cell-driven cartilage disturbances, probably through reduction of iNOS.
研究白细胞介素-4（IL-4）和IL-10在基础状态下以及IL-1和IL-17介导的软骨细胞代谢抑制中的作用。
将未接触过抗原的小鼠髌骨软骨外植体单独与IL-17和/或IL-1孵育，或先用IL-4和IL-10预处理。此外，将未接触过抗原的小鼠膝关节单独关节内注射IL-4和IL-10，或与IL-1联合注射。在完整的小鼠关节软骨中测量软骨细胞蛋白聚糖（PG）的合成。使用格里斯试剂测量一氧化氮（NO）水平。
IL-17是一种由CD4 + 活化记忆T细胞分泌的新型细胞因子，它抑制完整小鼠关节软骨中软骨细胞PG的合成，尽管其抑制作用不如IL-1强。在存在NO代谢抑制剂L-NIO（L-NS-[1-亚氨基乙基]鸟氨酸）的情况下，IL-17的抑制作用完全消除，并且IL-17仅轻微诱导iNOS（诱导型NO合酶）基因敲除小鼠髌骨软骨外植体中PG合成的抑制。这表明IL-17的抑制作用是由NO介导的。用IL-4预处理可显著降低IL-1或IL-17诱导的软骨细胞PG合成抑制，但IL-10预处理则无此作用。IL-4诱导的IL-1和IL-17对软骨细胞PG合成抑制作用的降低伴随着培养上清液中NO生成的减少。
IL-17在抑制软骨细胞PG合成中起作用。IL-4和IL-10对基础软骨细胞代谢无影响。然而，经IL-4预处理的软骨对IL-1和IL-17的抑制作用较不敏感。这表明IL-4在T细胞驱动的软骨紊乱中具有保护作用，可能是通过减少iNOS实现的。
