Ogawa N, Dang H, Lazaridis K, McGuff H S, Aufdemorte T B, Talal N
Department of Medicine, University of Texas Health Science Center at San Antonio 78284-7874, USA.
J Interferon Cytokine Res. 1995 Sep;15(9):759-67. doi: 10.1089/jir.1995.15.759.
Cytokines play a major role in tissue destruction caused by autoimmune dysregulation. In Sjögren's syndrome (SS) patients, salivary glands are the target organs for autoimmune tissue damage. In the present study, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to look for cytokine mRNA expressed in SS salivary glands. Focus score was used to determine the severity of the lesions. Cytokine production in supernatants of the salivary gland cell culture was measured by enzyme-linked immunosorbent assay (ELISA). Immunohistochemical staining was used to identify the local presence of transforming growth factor beta (TGF-beta). Interleukin (IL)-2, IL-6, and IL-10 mRNA were expressed in moderate to severe SS salivary gland lesions. TGF-beta mRNA was constitutively expressed in normal and SS salivary glands. In SS salivary gland cell cultures, IL-6 and IL-10 proteins were produced. TGF-beta production was reduced in high focus score SS glands. Normal and minimally involved SS salivary gland ductal epithelium and acinar cells were found to produce TGF-beta by immunostaining. In conclusion, an excess production of IL-2, IL-6, and IL-10 and a reduced production of the immunosuppressive cytokine, TGF-beta, may be responsible for the progression of the salivary gland lesion in SS. Specific immunotherapy can now be designed based on mechanisms to correct this cytokine imbalance and benefit patients with autoimmune diseases, such as SS.
细胞因子在自身免疫调节异常所致的组织破坏中起主要作用。在干燥综合征（SS）患者中，唾液腺是自身免疫性组织损伤的靶器官。在本研究中，采用逆转录聚合酶链反应（RT-PCR）来寻找SS唾液腺中表达的细胞因子mRNA。用焦点评分来确定病变的严重程度。通过酶联免疫吸附测定（ELISA）检测唾液腺细胞培养上清液中的细胞因子产生情况。采用免疫组织化学染色来鉴定转化生长因子β（TGF-β）的局部存在情况。白细胞介素（IL）-2、IL-6和IL-10 mRNA在中度至重度SS唾液腺病变中表达。TGF-β mRNA在正常和SS唾液腺中组成性表达。在SS唾液腺细胞培养物中，产生了IL-6和IL-10蛋白。在高焦点评分的SS腺体中，TGF-β的产生减少。通过免疫染色发现，正常和轻度受累的SS唾液腺导管上皮和腺泡细胞可产生TGF-β。总之，IL-2、IL-6和IL-10的过量产生以及免疫抑制细胞因子TGF-β的产生减少，可能是SS唾液腺病变进展的原因。现在可以基于纠正这种细胞因子失衡的机制设计特异性免疫疗法，使干燥综合征等自身免疫性疾病患者受益。
