Title:The Effect of Cyclosporine A on Dermal Fibroblast Cell - Transcriptomic Analysis of Inflammatory Response Pathway
Volume: 21
Issue: 12
Author(s): Grażyna Janikowska*, Ewa Kurzeja, Marcin Janikowski, Barbara Strzałka-Mrozik, Alina Pyka-Pająk and Tomasz Janikowski
Affiliation:
- Department of Analytical Chemistry, Medical University of Silesia in Katowice, Katowice,Poland
Keywords:
CsA, oligonucleotide microarray, profibrotic, proapoptotic, human dermal fibroblasts, genotoxic action.
Abstract:
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.