Portal tracts were enriched for immune system-related GO categories such Alvelestat concentration as immune system process (26% genes, adj. P = 1.8 × 10−5), immune response (17.1%,

adj. P = 4.1 × 10−3), cell adhesion (18.6% genes, adj. P = 4.9 × 10−4) and locomotion (11.4%, adj. P = 0.03) In particular, the portal tract was enriched for the expression of chemokine genes and their receptors (CCL2, CCL19, CKLF, CCR5, CXCR4). Consistent with the role of chemokines in trafficking inflammatory cells, genes found in innate immune phagocytic cells (e.g., lysozyme), were up-regulated in portal tracts, as were genes important in antigen-presenting cells (e.g., HLA-DQA1, HLA-DPA1). Genes associated with B-cells function (EBF1, BCL11B, PBXIP1, BCL2, BANK1) were differentially regulated with FDR < 0.05 but had an FC < 2. Molecules that form part of several downstream signaling cascades, such as IKBKB, and cell adhesion molecules such as ICAM1, were also up-regulated in the portal tracts at FDR < 0.05 but FC < 2. Of the 730 genes up-regulated in hepatic parenchyma, 725 were associated with GO categories. NVP-AUY922 datasheet In

contrast to portal tracts, only 43/725 (5.9%, adj. P = 1) were associated with the immune system process GO category and 35/725 (4.8%, adj. P = 0.82) were associated with immune response. The hepatic parenchyma immune related genes were primarily soluble immune proteins and/or acute phase reactants, such as complement factor B (FC = 7, FDR = 1.2 × 10−10) and mannose-binding lectin (FC = 2, FDR = 0.004). Of the immune Ixazomib cost genes that were up-regulated in parenchymal sections, several were well-described interferon-stimulated genes (ISGs), such as IFIT2 (FC = 2.6, FDR = 0.02), IFI6 (log2FC = 2.6, FDR = 8 × 10−4), and IFITM3 (FC = 7, FDR = 4 × 10−3). Among the genes up-regulated in parenchymal sections that were not related to immune function, the majority corresponded largely to GO:0055114, oxidation-reduction processes (19.6%, P = 4.8 × 10−49), and other metabolic functions.

Comparing portal tracts in PC tissues to those in NF tissues revealed that most up-regulation of immune process genes was due to portal tracts in the absence of fibrosis; 98 genes were up-regulated in portal tracts from NF tissues, whereas 79 genes were up-regulated in portal tracts from PC tissues (Fig. 6). GO categories relating to immune response were enriched in the 26 genes common to both groups. An enrichment of immune-related pathways was also observed in the 72 genes that were up-regulated only in portal tracts from NF tissues. These 72 included genes involved in T-cell activation and differentiation (e.g., NCK2, STAT5A, IL15) as well as cell adhesion molecules (CCL2, CCL18) and inflammasome-related genes (NLRC3, NLRC5).