Microarray Analysis of Leukocytapheresis-induced Changes in Gene Expression Patterns of Peripheral Blood Mononuclear Cells in Patients With Ulcerative Colitis

Abstract: To elucidate the molecular mechanisms involved in the therapeutic effects of leukocytapheresis (LCAP), we performed microarray analysis for gene expression patterns in peripheral blood mononuclear cells (PBMCs) before and after LCAP therapy in patients with ulcerative colitis (UC). Four patients with UC were enrolled. PBMCs were isolated from peripheral venous blood obtained within 5 min before and after the first session of LCAP therapy. Cells were stimulated with IL-1β for 12 h, and gene expression patterns were analyzed by an IntelliGene HS Human Expression Chip. The LCAP session reduced various genes, such as proinflammatory cytokines (IL-1α, IL-1β, IL-6, IL-8, TNF-α, and IFN-γ), cytokine receptors (IL-1R and IL-2Rα), chemokines, chemokine receptors, and intracellular signal transduction molecules. Genes which had increased after the LCAP session included those regulating anti-inflammatory cytokines and proteins (TGF-β1 and IL-R antagonist), receptors for anti-inflammatory cytokines (IL-10R and IL-4R), growth factor receptors (IGF-R1, R2) and antioxidant proteins. Total changes in gene expression patterns after LCAP session were a combination of a decrease in pro-inflammatory genes and an enhancement of anti-inflammatory genes. These changes may explain some parts of the mechanisms by which LCAP improves clinical symptoms of UC patients.