Kawamoto Minako, Matsui Eiko, Kaneko Hideo, Fukao Toshiyuki, Teramoto Takahide, Kasahara Kimiko, Kondo Naomi
Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu 501-1194, Japan.
Mol Med Rep. 2008 Nov-Dec;1(6):837-42. doi: 10.3892/mmr_00000037.
Interleukin (IL)-10 has anti-inflammatory activities in various immune reactions and plays an important role in the regulation of immune diseases. In the present study, we examined the role of IL-10 in atopic diseases. Peripheral blood mononuclear cells (PBMCs) from healthy control subjects, patients with atopic dermatitis and patients with bronchial asthma were cultured with lipopolysaccharide (LPS). The production of IL-10, IL-12 or IFN-γ by PBMCs stimulated with LPS was measured. Next, we investigated whether the haplotype in the IL-10 gene promoter region had an effect on the production of IL-10 by PBMCs. PBMCs from patients were cultured with phytohemagglutinin, to which recombinant human IL-10 had been added. IL-12, IFN-γ and IL-4 production by PBMCs was measured. β-lactoglobulin (BLG)-specific T cell clones were cultured with BLG peptide (P-17), antigen-presenting cells and recombinant human IL-10. The antigen-induced proliferation of the T cell clones and cytokine production were assayed. Results demonstrated that IL-10 production by LPS-stimulated PBMCs was lower in atopic patients than in healthy control subjects. Three different haplotypes in the IL-10 gene promoter region were detected. These haplotypes did not correlate with IL-10 production by PBMCs. IL-10 inhibited Th1 cytokine production by PBMCs, and also inhibited the antigen-induced proliferation of T cell clones and Th2 cytokine production. In conclusion, IL-10 inhibits both the production of Th1 and Th2 cytokines and the antigen-induced proliferation of T cell clones. Thus, IL-10 modulates other cytokines and plays an important role as an immune-modulator in the pathogenesis of atopic diseases.
白细胞介素(IL)-10在多种免疫反应中具有抗炎活性,在免疫疾病的调节中发挥重要作用。在本研究中,我们检测了IL-10在特应性疾病中的作用。将来自健康对照受试者、特应性皮炎患者和支气管哮喘患者的外周血单个核细胞(PBMC)与脂多糖(LPS)一起培养。测定LPS刺激的PBMC产生的IL-10、IL-12或IFN-γ。接下来,我们研究了IL-10基因启动子区域的单倍型是否对PBMC产生IL-10有影响。将患者的PBMC与添加了重组人IL-10的植物血凝素一起培养。测定PBMC产生的IL-12、IFN-γ和IL-4。用β-乳球蛋白(BLG)特异性T细胞克隆与BLG肽(P-17)、抗原呈递细胞和重组人IL-10一起培养。检测抗原诱导的T细胞克隆增殖和细胞因子产生。结果表明,LPS刺激的特应性患者PBMC产生的IL-10低于健康对照受试者。在IL-10基因启动子区域检测到三种不同的单倍型。这些单倍型与PBMC产生IL-10无关。IL-10抑制PBMC产生Th1细胞因子,也抑制抗原诱导的T细胞克隆增殖和Th2细胞因子产生。总之,IL-10抑制Th1和Th2细胞因子的产生以及抗原诱导的T细胞克隆增殖。因此,IL-10调节其他细胞因子,在特应性疾病的发病机制中作为免疫调节剂发挥重要作用。