Secretion of inflammatory factors from chondrocytes by layilin signaling
Secretion of inflammatory factors from chondrocytes by layilin signaling
复制标题
DOI：
10.1016/j.bbrc.2014.08.053
复制
发表时间：
2014-09-12
影响因子：
3.1
通讯作者：
Kato, Tomohiro
中科院分区：
文献类型：
--
作者：
Asano, Kota;Arito, Mitsumi;Kato, Tomohiro
Layilin (LAYN) 被认为参与细胞骨架结构的重组，与 merlin、radixin 和 talin 相互作用。此外，已知 LAYN 是透明质酸 (HA) 的受体之一。在类风湿性关节炎 (RA) 中，肿瘤坏死因子 α (TNF-α) 等炎性细胞因子已知发挥病理作用。据推测，低分子量的 HA 会加剧 RA 的炎症。在这种情况下，HA受体的数量和功能的差异将影响RA炎症的严重程度。软骨细胞在维持关节软骨中起关键作用并在 RA 中受到影响，至少表达多种 HA 受体，如 CD44 和 LAYN。然而，人们对LAYN在关节软骨细胞中的作用和调节知之甚少。为了阐明LAYN在软骨细胞中的调节，我们研究了TNF-α是否影响人关节软骨细胞中LAYN的表达水平。接下来，为了阐明 LAYN 在软骨细胞中的特异性作用，我们使用软骨肉瘤细胞系研究了抗体与 LAYN 胞外结构域的结合是否影响炎症细胞因子的分泌。结果，我们发现TNF-α上调软骨细胞中LAYN的表达水平。此外，还发现 LAYN 信号传导可增强细胞中炎症因子 IL-8 和补体 5 (C5)/C5a 的分泌。我们的结果表明，LAYN 可能参与 RA 和 OA 等关节疾病的炎症增强和软骨退化。 (C) 2014 Elsevier Inc. 保留所有权利。
Layilin (LAYN) is thought to be involved in reorganization of cytoskeleton structures, interacting with merlin, radixin, and talin. Also, LAYN is known to be one of the receptors for hyaluronic acid (HA).In rheumatoid arthritis (RA), inflammatory cytokines like tumor necrosis factor alpha (TNF-alpha) have been known to play pathological roles. HA with low molecular weight is speculated to exacerbate inflammation in RA. In this context, differences of quantity and functions of HA receptors would affect the severity of inflammation in RA. Chondrocytes, which play critical roles in maintaining articular cartilage and are affected in RA, express at least kinds of HA receptors like CD44 and LAYN. However, roles and regulation of LAYN in articular chondrocytes have been poorly understood.To clarify regulation of LAYN in chondrocytes, we here investigated whether TNF-alpha affected expression levels of LAYN in human articular chondrocytes. Next, to clarify LAYN-specific roles in chondrocytes, we investigated whether binding of antibodies to the extracellular domain of LAYN affected secretion of inflammatory cytokines using a chondrosarcoma cell line. As a result, we found that TNF-alpha up-regulated expression levels of LAYN in the chondrocytes. Further, the LAYN signaling was found to enhance secretion of inflammatory factors, IL-8 and complement5 (C5)/C5a, from the cells. Our results indicate that LAYN would be involved in the enhancement of inflammation and degradation of cartilage in joint diseases such as RA and OA. (C) 2014 Elsevier Inc. All rights reserved.