Background: The first immunosuppressive drug - cyclosporine A (CsA) has many unquestioned merits in maintaining organ transplants in patients, as well as, in the treatment of many inflammatory diseases, also associated with cutaneous manifestations. The main task of this drug is to suppress the inflammatory response at the sites of action, which is not well known.

Objective: The objective of this study was to evaluate the influence of CsA in therapeutic concentration on the expression of genes associated with the inflammatory response pathway in normal human dermal fibroblasts (NHDF; CC-2511), and this study attempted to determine the mechanism of its action.

Methods: The cytotoxicity MTT test was performed. The expression of the inflammatory response pathway genes was determined using HG-U133A_2.0 oligonucleotide microarrays. Statistical analysis was performed by GeneSpring 13.0 software using the PL-Grid platform.

Results: Among the 5,300 mRNA, only 573 were changed significantly in response to CsA compared to the control fibroblasts (P≤0.05). CsA inhibited the expression of most genes associated with the inflammatory response in NHDFs. There were only 19 genes with a fold change (FC) lower than -2.0, among which EGR1, FOS, PBK, CDK1 and TOP2A had the lowest expression, as did CXCL2 which can directly impact inflammation. Furthermore, ZNF451 was strongly induced, and COL1A1, COL3A1, IL33, TNFRSFs were weakly up-regulated (FC lower than 2.0).

Conclusion: The CsA in therapeutic concentration influences the genes linked to the inflammatory response (in the transcriptional level) in human dermal fibroblasts. The findings suggest that the potential mechanism of CsA action in this concentration and on these genes can be associated with a profibrotic and proapoptotic, and genotoxic effects.

背景：第一种免疫抑制药-环孢素A（CsA）在维持患者器官移植以及治疗许多炎症性疾病（也与皮肤表现有关）方面具有许多毋庸置疑的优点。这种药物的主要任务是抑制作用部位的炎症反应，这是众所周知的。

目的：本研究的目的是评估治疗浓度的CsA对正常人真皮成纤维细胞（NHDF; CC-2511）炎症反应途径相关基因表达的影响，并试图确定其机制。它的行动。

方法：进行细胞毒性MTT试验。使用HG-U133A_2.0寡核苷酸微阵列确定炎症反应途径基因的表达。使用PL-Grid平台通过GeneSpring 13.0软件进行统计分析。

结果：在5300个mRNA中，与对照成纤维细胞相比，只有573个对CsA的响应发生了显着变化（P≤0.05）。CsA抑制了与NHDF中炎症反应相关的大多数基因的表达。折叠变化（FC）低于-2.0的基因只有19个，其中EGR1，FOS，PBK，CDK1和TOP2A的表达最低，而CXCL2可以直接影响炎症。此外，强烈诱导ZNF451，并且COL1A1，COL3A1，IL33，TNFRSF弱上调（FC低于2.0）。

结论：治疗浓度的CsA影响与人类皮肤成纤维细胞炎症反应相关的基因（转录水平）。这些发现表明，在这种浓度下以及对这些基因的CsA作用的潜在机制可能与促纤维化和促凋亡以及遗传毒性有关。