Henrotin Y E, De Groote D D, Labasse A H, Gaspar S E, Zheng S X, Geenen V G, Reginster J Y
Cartilage Metabolism Research Unit, University Hospital, Sart-Tilman, CHU, Liège, Belgium.
Osteoarthritis Cartilage. 1996 Sep;4(3):163-73. doi: 10.1016/s1063-4584(96)80012-4.
Cytokines are potent regulators of the chondrocyte functions. Some of them are produced by chondrocytes and interact to regulate cartilage metabolism. In this study, we investigated the production of interleukin-1 beta (IL-1 beta), IL-6, IL-8 and leukemia inhibitory factor (LIF) by human chondrocytes and examined the modulation of their secretion by exogenous cytokines. Human articular chondrocytes were isolated from their extracellular matrix by a triple successive enzymatic digestion of the cartilage. Subsequently, chondrocytes were stimulated by increased amounts of human recombinant cytokines [IL-1 beta, tumour necrosis factor alpha (TNF alpha), IL-8, LIF, IL-6]. IL-1 beta, IL-6, IL-8 and LIF were assayed into culture media and inside cell extracts by specific enzyme amplified sensitivity immunoassays (EASIAs). Under these experimental conditions, we have identified various interactions between cytokines. IL-beta and TNF alpha highly stimulated IL-6, LIF and IL-8 productions. IL-6 decreased IL-8 synthesis and increased LIF production. IL-8 slightly enhanced IL-6 production. Finally, LIF stimulated IL-1 beta, IL-6 and IL-8 productions. Using neutralizing antibodies against IL-1, we demonstrated that the effects of LIF were secondary to the stimulation by LIF of IL-1 beta production by the chondrocytes. In conclusion, chondrocytes secrete a variety of immunocompetent cytokines including IL-1 beta, IL-6, IL-8 and LIF that can interact to regulate chondrocytes metabolism. These results also define new biological activities of LIF and IL-6, and raise questions concerning their role in the pathogenesis of joint diseases.
细胞因子是软骨细胞功能的强效调节剂。其中一些由软骨细胞产生并相互作用以调节软骨代谢。在本研究中，我们调查了人软骨细胞白细胞介素-1β（IL-1β）、IL-6、IL-8和白血病抑制因子（LIF）的产生情况，并检测了外源性细胞因子对其分泌的调节作用。通过对软骨进行连续三次酶消化从细胞外基质中分离出人关节软骨细胞。随后，用人重组细胞因子[IL-1β、肿瘤坏死因子α（TNFα）、IL-8、LIF、IL-6]的增加量刺激软骨细胞。通过特异性酶扩增敏感性免疫测定法（EASIAs）测定培养基和细胞提取物中的IL-1β、IL-6、IL-8和LIF。在这些实验条件下，我们确定了细胞因子之间的各种相互作用。IL-β和TNFα高度刺激IL-6、LIF和IL-8的产生。IL-6减少IL-8的合成并增加LIF的产生。IL-8轻微增强IL-6的产生。最后，LIF刺激IL-1β、IL-6和IL-8的产生。使用抗IL-1的中和抗体，我们证明LIF的作用继发于LIF对软骨细胞产生IL-1β的刺激。总之，软骨细胞分泌多种具有免疫活性的细胞因子，包括IL-1β、IL-6、IL-8和LIF，它们可以相互作用调节软骨细胞代谢。这些结果还定义了LIF和IL-6的新生物学活性，并提出了它们在关节疾病发病机制中的作用问题。
