Department of Rheumatology, Faculty of Medicine, 19 Mayis University, Samsun, Turkey.
Inflammation. 2015 Feb;38(1):252-9. doi: 10.1007/s10753-014-0028-6.
Epidermal growth factor receptor (EGFR) and its ligands are commonly expressed by synovial cells. The aim of the present study was to detect the potential effect of lapatinib an inhibitor of EGFR tyrosine kinases on collagen-induced arthritis. Thirty Wistar albino female rats were randomized into three groups. Arthritis was induced by intradermal injection of chicken type II collagen with incomplete Freund's adjuvant. Serum TNF-α, IL-17, and malondialdehyde (MDA) levels were analyzed. Tissue superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) activities, and nuclear factor erythroid 2-related factor-2 (Nrf2) and heme oxgenase-1 (HO-1) expressions were determined. TNF-α, IL-17 and MDA levels, and Nrf2 and HO-1 expressions were lower in lapatinib-treated (30 mg/kg/day) group compared to sham group, while SOD, catalase, and GPx activities were higher (p < 0.05). Moreover, lapatinib ameliorated perisynovial inflammation and cartilage-bone destruction (p < 0.001). In conclusion, EGFR may have prominent pathogenic role and lapatinib may be an effective therapeutic option for arthritis.
表皮生长因子受体 (EGFR) 及其配体通常由滑膜细胞表达。本研究旨在检测 EGFR 酪氨酸激酶抑制剂拉帕替尼对胶原诱导性关节炎的潜在作用。将 30 只 Wistar 白化雌性大鼠随机分为三组。关节炎通过皮内注射鸡 II 型胶原和不完全弗氏佐剂诱导。分析血清 TNF-α、IL-17 和丙二醛 (MDA) 水平。测定组织超氧化物歧化酶 (SOD)、过氧化氢酶和谷胱甘肽过氧化物酶 (GPx) 活性,以及核因子红细胞 2 相关因子 2 (Nrf2) 和血红素加氧酶-1 (HO-1) 的表达。与假手术组相比,拉帕替尼(30mg/kg/天)治疗组的 TNF-α、IL-17 和 MDA 水平以及 Nrf2 和 HO-1 表达较低,而 SOD、过氧化氢酶和 GPx 活性较高(p<0.05)。此外,拉帕替尼改善了滑膜周围炎症和软骨-骨破坏(p<0.001)。总之,EGFR 可能具有突出的致病作用,拉帕替尼可能是关节炎的有效治疗选择。