Table 3.
The inflammatory signaling pathways and related gene transcripts affected by daily injection of PYS solution compared to Sham
| Signaling pathways (p value) | Up regulated genes | Down regulated genes |
|---|---|---|
| Granulocyte adhesion and diapedesis (1 × 10 −11) | C5AR1, CCL2, CCL4, CCL19, CCL21, CXCL13, CXCL14, CXCR2, EZR, IL1B, IL1RN, ITGB2, MMP9, MMP16, SELL, TNF, TNFRSF11B, VCAM1 | CLDN5, CXCL2, CXCR4, ICAM2, IL33, IL1RAPL1, MMP27, THY1 |
| Agranulocyte adhesion and diapedesis (1 × 10 −10) | AOC3, C5AR1, CCL2, CCL4, CCL19, CCL21, CXCL13, CXCL14, CXCR2, EZR, IL1B, IL1RN, ITGB2, MMP9, MMP16, SELL, TNF, VCAM1 | CD34, CLDN5, CXCL2, CXCR4, ICAM2, IL33, MMP27 |
| Role of hypercytokinemia/hyperchemokinemia in the pathogenesis (3 × 10 −8) | CCL2, CCL4, CCR1, CCR5, IL1B, IL1RN, TNF | IL6, IL33 |
| Acute phase response signaling (1 × 10 −6) | A2M, AGT, C3, C4BPA, CFB, FGG, HP, IKBKE, IL1B, KLKB1, RBP1, RBP4, SERPINA3, SERPINE1, TNF, TNFRSF11B | IL6, IL33, RB97 |
| Complement (1 × 10 −5) | C3, C6, C4BPA, C5AR1, CFD, ITGB2, CFB, ITGAM | – |
| IL-10 signaling (1 × 10 −5) | IKBKE, CCR1, CCR5, CD14, FCGR2B, IL1B, IL1RN, TNF | IL6, IL33, IL1RAPL1 |
| Differential regulation of cytokine production in MΦ and Th cell (0.0001) | CCL2, CCL4, IL1B, LCN2, TNF | – |
| B cell development (0.001) | HLA-DRA, HLA-DRB5, IL7, IL7R, PTPRC | – |
| Inhibition of matrix metalloproteinase (0.002) | A2M, MMP9, MMP16, TIMP1 | MMP27, TIMP4 |
| Cross talk between DCs and NK cells (0.0025) | HLA-DRA, HLA-DRB5, TNF, TLR3 | IL6, IL4, FSCN1, CAMK2D |
| TREM1 signaling (0.0025) | CCL2, CIITA, FCGR2B, IL1B, NLRP3, TLR3, TNF | IL6 |
| ICOS/ICOSL signaling in Th cells (0.00316) | HLA-DRA, HLA-DRB5, IKBKE, ITK, PTPRC, GRAPB2 | Calm1, CAMK2D, LAT |
| Antigen presentation pathway (0.00316) | HLA-DRA, HLA-DRB5, CD74, CIITA | – |
| IL-6 signaling (0.01) | IKBKE, A2M, CD14, IL1B, IL1RN, TNF, TNFRSF11B | IL6, IL33, IL1RAPL1 |
| CD28 signaling in Th cells (0.0126) | HLA-DRA, HLA-DRB5, PTPRC, PAK1, GRAP2, IKBKE, ITK | Calm1, LAT |
| Toll-like receptor signaling (0.0126) | CD14, IL1B, IL1RN, TLR3, TNF, UBD | IL33 |
| IL-17 signaling in fibroblast (0.0501) | IKBKE, CCL2, LCN2 | IL6 |
| MIF-mediated glucocortical regulation (0.0501) | CD74, PLA2G2A, PLA2G5, CD14 | – |
| MIF regulation of innate immunity (0.0501) | CD74, PLA2G2A, PLA2G5, CD14 | – |
| HMGB1 signaling (0.0501) | VCAM1, TNFRSF11B, TNF, SERPINE1, IL1B, CCL2 | IL6, IL4 |
| Nur 77 signaling in T cells (0.0631, NS) | HLA-DRA, HLA-DRB5 | Calm1, CASP3 |
The affected signaling pathways were ranked from the most (top) to the least significant (bottom) based on the p value
DC dendritic cell, NK natural killer, Th T helper, MΦ macrophage, ICOS inducible costimulator, ICOSL inducible costimulatory ligand, TREM1 triggering receptor expressed on myeloid cells 1, MIF macrophage migration inhibitory factor, HMGB1 high mobility group box 1, NS not significant