Mustafa W, Zhu J, Deng G, Diab A, Link H, Frithiof L, Klinge B
Department of Periodontology, Faculty of Odontology, Huddinge University Hospital, Karolinska Institute, Sweden.
Clin Exp Immunol. 1998 Jun;112(3):389-96. doi: 10.1046/j.1365-2249.1998.00609.x.
MRL/Mp-lpr/lpr (MRL/lpr) mice spontaneously develop destructive inflammation of the salivary and lachrymal glands resembling Sjögren's syndrome (SS), representing an animal model to study this disease. We used in situ hybridization with synthetic radiolabelled oligonucleotide probes to examine expression of mRNA encoding pro- and anti-inflammatory cytokines in submandibular glands of 2, 3, 4 and 5-month-old MRL/lpr mice. Phenotypic composition of submandibular gland infiltrates was evaluated by immunohistochemistry. Cells expressing tumour necrosis factor-alpha (TNF-alpha), IL-1beta, IL-6 and IL-12 mRNA were strongly up-regulated at about the time of onset of sialoadenitis, suggesting a role of these cytokines in development of the disease. Interferon-gamma (IFN-gamma) and cytolysin mRNA-expressing cells were gradually up-regulated over the disease course up to 5 months of age, the time when sialoadenitis is at its height, favouring a role of these cytokines in progression of the disease as well. Low levels of IL-10 and transforming growth factor-beta (TGF-beta) mRNA-expressing cells were observed at 2, 3 and 4 months of age, and were almost undetectable at 5 months. Maximum levels of CD4+, CD8+ and interdigitating/dendritic cells, as well as of MHC class II and MHC class I expression were seen at 3 months, with CD4+ outnumbering CD8+ cells. Maximum levels of macrophages were seen at 4 months of age. These data argue for a major role of the proinflammatory cytokines TNF-alpha, IL-1beta, IL-6, IL- 12, IFN-gamma and cytolysin in initiation and perpetuation of autoimmune sialoadenitis in MRL/lpr mice, probably in conjunction with an insufficiency of the anti-inflammatory cytokines TGF-beta and IL-10.
MRL/Mp-lpr/lpr（MRL/lpr）小鼠会自发出现类似于干燥综合征（SS）的唾液腺和泪腺破坏性炎症，是研究该疾病的动物模型。我们使用合成放射性标记寡核苷酸探针进行原位杂交，以检测2、3、4和5月龄MRL/lpr小鼠下颌下腺中促炎和抗炎细胞因子编码mRNA的表达。通过免疫组织化学评估下颌下腺浸润的表型组成。在涎腺炎发病时，表达肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和白细胞介素-12（IL-12）mRNA的细胞强烈上调，表明这些细胞因子在疾病发展中起作用。表达干扰素-γ（IFN-γ）和溶细胞素mRNA的细胞在疾病进程中逐渐上调，直至5月龄，此时涎腺炎最为严重，这也表明这些细胞因子在疾病进展中起作用。在2、3和4月龄时观察到表达白细胞介素-10（IL-10）和转化生长因子-β（TGF-β）mRNA的细胞水平较低，在5月龄时几乎检测不到。在3月龄时观察到CD4 +、CD8 +和指状/树突状细胞以及MHC II类和MHC I类表达的最高水平，其中CD4 +细胞数量超过CD8 +细胞。在4月龄时观察到巨噬细胞的最高水平。这些数据表明促炎细胞因子TNF-α、IL-1β、IL-6、IL-12、IFN-γ和溶细胞素在MRL/lpr小鼠自身免疫性涎腺炎的起始和持续中起主要作用，可能与抗炎细胞因子TGF-β和IL-10不足有关。
