Additionally, miR-192 significantly alters expression of NOD2 mRNA and protein and significantly reduces phosphorylation of NF-[kappa]B and expression of IL-8 and CXCL3
Based on "omics" data which has been experimentally validated, molecules in circulating monocytes that are relevant to BMD may be categorized into processes such as apoptosis/survival (PLK3 and HSPB1), migration/chemotaxis (CXCL3
, GSN, and HSPB1), adhesion (RSU1, HSPB1), transendothelial migration (ANXA2, HSPB1), differentiation into osteoclasts (STAT1, GBP1, ANXA2, and GSN), and other miscellaneous processes such as histamine biosynthesis (HDC), glucocorticoid sensitivity (GCR), regulation of oxidative stress (SOD2, GPX1), and protein folding (P4HB) and multifunctional molecules, miR-133a and miR422a (complete list of molecules identified and validated in Table 1).
Several papers demonstrated that TNF[alpha] in KC regulates different genes involved in inflammation and angiogenesis, such as IL-1, ICAM-1, VEGF [29, 30], TGF-[beta], chemokines (CCL20, CCL27, CCL5, CCL2, CXCL10, and CXCL11), and members of the CXCL8 family, including CXCL1, CXCL2, and CXCL3
[10, 22, 23].
Fifteen module-related DEGs marked as bold in Table 4 were thus obtained, including CXCL2, CXCL1, BDKRB1, LPAR1, CXCL3
, FYN, COL6A2, COL18A1, COL13A1, COL5A1, TUBA1A, FDFT1, SQLE, LSS, and CDK9.
Likewise, among the top 20 upregulated genes we found 11 Wnt/[beta]-catenin target genes (Table 1 and Supplementary Table 3), including the palmitoleoyl-protein carboxylesterase Notum (ID: 303743; nominal p value = 1.5 x [10.sup.-5]; FC = 14.1), Lef1 (ID: 161452; nominal p value = 1.7 x [10.sup.-5]; FC = 2.1), Axin2 (ID: 29134; nominal p value = 1.2 x [10.sup.-4]; FC = 3.5), and the chemokine (C-X-C motif) ligand 3 Cxcl3
(ID: 171551; nominal p value = 5.2 x [10.sup.-4]; FC = 4.6).
The genes examined were tumor necrosis factor alpha (TNF-[alpha]), interferon gamma (IFN-[gamma]), and interleukin-6 (IL-6) for inflammatory cytokines and monocyte chemotactic protein-1 (MCP-1) and Chemokine (C-X-C motif) ligand 3 (Cxcl3
) for chemokines.
gene, belonging to chemokine family, is related to inflammatory response.
The genes that were downregulated by more than 2fold included the genes encoding the cytokines chemokine (C-X-C motif) ligand 3 (CXCL3
) and caprin family member 2 (CAPRIN2), the transporter component of the oligomeric golgi complex 5 (COG5), and various genes associated with transcription, kinase, ion binding, and nucleotide metabolism.
Name References Cytokines TNF-[alpha] (+) [69-71] IL-1 (+) [72-74] IL-6  IL-8 (CXCL18) [75, 76] IL-15  IL-17  IL-18 (+) [79-82] Chemokines CXCL1 [83, 84] CXCL2 [83, 84] CXCL3
[83-86] CXCL5 [83, 84] CXCL6 [83, 84] CXCL7 [83, 84] CXCL9  CXCL12 (SDF-1) [87, 88] CCL2 (MCP-1) [89, 90] (+) Also antiangiogenic activity has been reported.
These include Bcl2, CCND1, CXCL1, CXCL3
, IL-18, IL-6, IRF1, NF-KB1, PTGS2, TNF-[alpha], TNFSF10, TRADD, and TRAF1.
Among genes ascribed to the immune response, twenty Th17-lymphocyte-related genes were upregulated including interleukin 6 signal transducer, IL6ST, chemokine (C-C motif) ligand 20, CCL20, suppressor of cytokine signaling 3, SOCS3, chemokine (C-X-C motif) ligand 1, CXCL1, chemokine (C-X-C motif) ligand 2, CXCL2, chemokine (C-X-C motif) ligand 3, CXCL3
, inducible T cell costimulator, ICOS, intercellular adhesion molecule 1, ICAM1, interleukin 8, IL-8, interleukin 1 beta, and IL-1B (see also Table 2).
The liver transcriptional expressions of CXCL1, CXCL2, CXCL3
, CXCL5, CCL2, and CCL6 significantly increased in WT and IL-33 KO mice during L2-MHV3-induced hepatitis compared to those in control PBS-injected mice as soon as 48 h PI and at 72 h PI (Figures 6(c), 6(d), 6(e), 6(f), 6(g), and 6(h)).