Department of Dermatology, University Hospital Tuebingen, Tuebingen, Germany.
University Eye Hospital Tuebingen, Tuebingen, Germany.
Ocul Immunol Inflamm. 2022 Aug;30(6):1369-1377. doi: 10.1080/09273948.2021.1873396. Epub 2021 Apr 1.
The aim is to unravel the mechanism of mesalazine (5-ASA) on proinflammatory cytokines in PBMCs of patients with HLA-B27 +and HLA-B27 -acute anterior uveitis (AAU), and whether this may explain the different effects of 5-ASA in both disoders.
PBMCs from 12 HLA-B27+ and 4 HLA-B27- AAU patients were preincubated with 5-ASA and stimulated with LPS. As mesalazine (5-ASA) could be involved in ER stress, proinflammatory and ER stress-associated cytokines and markers were measured.
Mesalazine (5-ASA) suppressed IL-6 mRNA in healthy donors and in HLA-B27+ and HLA-B27- patients but did not lead to induction and secretion of IL-1β. In HLA-B27 + or - patients the ER stress-associated markers CHOP (DDIT3) and ATF6 were suppressed.
Here we show that mesalazine (5-ASA) inhibits the transcription of proinflammatory and (ER) stress associated cytokines and markers, independently of the HLA-B27 status. Results show the similarities of both AAU types but do not decipher the mechanism why the HLA-B27 status determines the therapeutic response to mesalazine in AAU.
本研究旨在探讨美沙拉嗪（5-ASA）对 HLA-B27+和 HLA-B27-急性前葡萄膜炎（AAU）患者 PBMC 中促炎细胞因子的作用机制，以及这是否可以解释 5-ASA 在两种疾病中的不同作用。
用 LPS 刺激预孵育了美沙拉嗪（5-ASA）的 12 例 HLA-B27+和 4 例 HLA-B27-AAU 患者的 PBMC。由于美沙拉嗪（5-ASA）可能参与内质网应激，因此测量了促炎和 ER 应激相关细胞因子和标志物。
美沙拉嗪（5-ASA）抑制了健康供体以及 HLA-B27+和 HLA-B27-患者的 IL-6 mRNA，但并未导致 IL-1β的诱导和分泌。在 HLA-B27+或 -患者中，与 ER 应激相关的标志物 CHOP（DDIT3）和 ATF6 受到抑制。
本研究表明，美沙拉嗪（5-ASA）可抑制促炎和（ER）应激相关细胞因子和标志物的转录，而与 HLA-B27 状态无关。结果显示了两种 AAU 类型的相似性，但并未阐明为什么 HLA-B27 状态决定了美沙拉嗪在 AAU 中的治疗反应的机制。
