Screening of key genes and inflammatory signalling pathway involved in the pathogenesis of HLA-B27-associated acute anterior uveitis by gene expression microarray

Abstract

To investigate the genes and signalling pathways located upstream of the inflammatory processes in human leukocyte antigen (HLA)-B27-associated acute anterior uveitis by gene expression microarray. Experimental study. HLA-B27-positive and-negative monocytes isolated from human peripheral blood were stimulated with Vibrio cholera lipopolysaccharide (LPS). Gene expression microarrays were used to identify the differentially expressed genes. Differentially expressed (DE) genes were testified by real-time PCR and analyzed by a series of bioinformatics-based techniques such as Gene Ontology, Kyoto Encyclopedia of Genes and Genomes. Gene expression microarray analysis revealed marked differences between HLA-B27-positive acute anterior uveitis (AAU) and HLA-B27-negative healthy control peripheral monocytes in the genes that were upregulated in response to LPS stimulation with 1105 genes and 25 genes respectively. Gene Ontology enrichment and pathway analysis indicated that genes participating in protein transport and folding were essential to the inflammatory process. The LPS receptor-Toll-like receptor (TLR)4 induced TLR signalling pathway and pathway related to Vibrio cholerae infection were located upstream of the network and contribute to the overall response. Among the DE genes, PIK3CA, PIK3CB, AKT3, and MAPK1 might play critical roles in inflammation. Equivalent LPS stimulation induces a different response in HLA-B27-positive peripheral monocytes compared to normal control, suggesting that the TLR pathway is involved in the pathogenesis of HLA-B27-associated AAU.