| Summary: | 碩士 === 國立臺灣大學 === 臨床醫學研究所 === 103 === Purpose
To determine the dynamic changes of NF-κB-related microRNAs and cytokines in the course of experimental autoimmune anterior uveitis (EAAU) and elucidate the possible immunopathogenesis.
Materials and methods
Uveitis was induced in Lewis rats with bovine melanin-associated antigen. The clinical scoring of the inflammatory activity of the anterior chamber and leukocyte quantification in aqueous humor was done. RNA extraction from iris/ciliary body, and popliteal lymph nodes was performed to reveal the dynamic changes of 8 target miRNAs (miR-155-5p, miR-146a-5p, miR-182-5p, miR-183-5p, miR-147b, miR-21-5p, miR-9-3p, and miR-223-3p) and mRNAs of 6 cytokines (IFN-γ, IL-17, IL-12p35, IL-1β, IL-6, IL-10). miRNA in situ hybridization and ELISA quantification of cytokines were performed to confirm the results.
Results
The disease activity and leukocyte quantification was maximal on day 15 following immunization. miRNA profiling revealed down-regulation of miR-146a-5p, miR-155-5p, miR-223-3p and miR-147b, and up-regulation of miR-182-5p, miR-183-5p, and miR-9-3p. Cytokines analysis disclosed IFN-γ, IL-17, IL-12p35, IL-1β, and IL-6 over-expression with IL-10 down-regulation.
Conclusion
Dynamic changes of miRNAs were present in the EAAU course. By initiating NF-κB signaling, expressions of downstream cytokines and effector cells of Th17 and Th1 lineage were sequentially activated, and contributed to the disease.
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