Department of Histology and Embryology, Faculty of Medicine, Cukurova University, Adana, Turkey.
Department of Histology and Embryology, Faculty of Veterinary, Cukurova University, Adana, Turkey.
Int Immunopharmacol. 2024 Dec 25;143(Pt 2):113439. doi: 10.1016/j.intimp.2024.113439. Epub 2024 Oct 22.
Rheumatoid arthritis (RA) is a multifactorial autoimmune disease that affects the joints of approximately 1 % of the population worldwide and is seen 2-4 times less in males. INSL3 is a gender-specific peptide hormone produced much higher in males than in females and may have an anti-inflammatory role in RA. So, in this study, it was aimed to determine the possible anti-inflammatory effect and dose of insulin-like factor-3(INSL3) in an experimental Complete Freund's adjuvant(CFA)-induced RA male rat model and lipopolysaccharide(LPS)-induced macrophage cell line and compare it with prednisolone therapy. For in vivo experiments, 48 male mice were randomly divided into 6 groups with 8 subjects in each group: Control group, Arthritis group, Arthritis + Prednisolone(10 mg/kg) group, Arthritis + INSL3(0.08-0.8-8 μg/day) groups. Joint tissue samples obtained from sacrificed subjects were examined by histochemical and immunohistochemically methods after biometric analyses, arthritis severity scoring, and thermal latency experiments. LPS-induced macrophage cells were also treated with prednisolone(1 µg/ml) and INSL3(50-100-200 nM). Cell viability, cell morphology, and TNF-α and IL-6 immune reactivity were evaluated. According to the data obtained from in vivo analyses, it was seen that INSL3 reduced the paw diameter and arthritis severity scoring, degenerative changes, and inflammation and increased the thermal latency, compared to the arthritis group, although not as much as the prednisolone treatment group. In vitro analyses showed that high doses of INSL3 had positive effects on cell viability, morphology, TNF-α, and IL-6 immune reactivity. In conclusion, it was determined that the anti-inflammatory effect of INSL3 was not as pronounced as prednisolone, but it had a more favorable impact on macrophage cell viability and morphology. It was concluded that INSL3 may be a protective therapeutic agent in combination with existing treatment protocols in treating many autoimmune diseases.
类风湿关节炎（RA）是一种多因素自身免疫性疾病，影响全球约 1%的人口，男性发病率低 2-4 倍。胰岛素样因子 3（INSL3）是一种性别特异性肽类激素，男性产生量明显高于女性，可能在 RA 中具有抗炎作用。因此，本研究旨在确定胰岛素样因子 3（INSL3）在实验性完全弗氏佐剂（CFA）诱导的 RA 雄性大鼠模型和脂多糖（LPS）诱导的巨噬细胞系中的可能抗炎作用和剂量，并与泼尼松龙治疗进行比较。在体内实验中，将 48 只雄性小鼠随机分为 6 组，每组 8 只：对照组、关节炎组、关节炎+泼尼松龙（10mg/kg）组、关节炎+INSL3（0.08-0.8-8μg/天）组。在生物计量分析、关节炎严重程度评分和热潜伏期实验后，通过组织化学和免疫组织化学方法检查处死动物的关节组织样本。还将 LPS 诱导的巨噬细胞用泼尼松龙（1μg/ml）和 INSL3（50-100-200nM）处理。评估细胞活力、细胞形态以及 TNF-α 和 IL-6 免疫反应性。根据体内分析获得的数据，与关节炎组相比，INSL3 降低了爪直径和关节炎严重程度评分、退行性变化和炎症，并增加了热潜伏期，尽管不如泼尼松龙治疗组明显。体外分析表明，高剂量的 INSL3 对细胞活力、形态、TNF-α 和 IL-6 免疫反应性有积极影响。总之，确定 INSL3 的抗炎作用不如泼尼松龙明显，但对巨噬细胞活力和形态有更有利的影响。结论是，INSL3 可能是一种保护性治疗剂，可与现有治疗方案联合用于治疗许多自身免疫性疾病。
