Table II. Summary of gene expression in IBD along with functions and transcriptional regulation.
Genes were quantified in this study with real time RT-PCR using FFPE colon biopsy samples from active UC (aUC), active CD (aCD), quiescent/ histologically normal-appearing colon from UC (qUC), and quiescent CD (qCD).
| Category | Transcription Regulation |
Function | Gene | Active UC |
Quiescent UC |
Active CD |
Quiescent CD |
|---|---|---|---|---|---|---|---|
| Cytokines | TLR/NFκB | +NF-κB/Apoptosis | TNF-α | ++ | NC | ++ | NC/+ |
| NF-kB/AP1 | +Neutroph/CXCR1/2 | IL-8 | +++ | NC | +++ | NC | |
| NF-κB/STAT3 | +NF-κB | IL-17 | +++++ | NC | ++++ | NC | |
| * NF-kB | +STAT3,gp130, RAS | IL-6 | +++ | NC | ++++ | NC | |
| * TLRs, STAT1,IRF | +STAT4,Th1/Th17 | IL-12/23 p40 | + | NC | +++ | NC | |
| * STAT4 | +STAT1/STAT2 | IFN-γ | NC/+ | NC | ++ | NC/+ | |
| Sp1/3, Antigen | +STAT6/PI3K | IL-13 | +++ | + | NC | NC | |
| TRAF6/NF-κB/AP1 | +NF-κB/st2/MAPK | IL-33 | ++ | + | + | NC | |
| * Multiple1 | +STAT3, +Treg | IL-10 | +++ | NC | NC/+ | NC | |
| Activation/Secretion | +SMADs, +Treg | TGF-β1 | + | NC | NC/+ | NC | |
|
Transcription
Factors |
STAT1/NFκB | +IFNγ, Th1 | IRF-1 | NC | NC | +++ | NC |
| STAT4/STAT1 | +Th1 Phenotype | T-bet | NC | NC | + | NC | |
| STAT6 | +Th2 Phenotype | GATA3 | + | NC | ↓ | NC | |
| * NA | Multiple | STAT3 | NC | NC | ↓ | NC | |
| SMAD1-7/STAT5 | +Tregs | FOXp3 | NC/+ | ↓ | NC/+ | NC | |
|
Regulators of
Signaling |
* NA | Kinase+ STAT1/3/4/6 | JAK2 | NC | NC | NC | NC |
| STAT3/STAT1 | (-) JAK1/2/3, STAT1 | SOCS1 | NC/+ | NC | ++ | NC | |
| STAT3/STAT1 | (-) JAK2/STAT3 | SOCS3 | +++ | NC | + | NC | |
| * NFκB | (-)STAT1,ERK,p38 | PTPN2 | NC/+ | NC | NC/+ | NC | |
| Methylation, STATs | (-) STAT1/3/6/NF-kB | SHP-1 | ↓ | ↓ | ↓ | NC | |
| NA | (-) STAT1/3,+ STAT5 | SHP-2 | NC | NC | NC | NC | |
| Chemokines | * NFκB | + MΦs/CCR2 | MCP-1 | +++ | NC/+ | +++ | NC/+ |
| MΦ activation | MCP-1 Receptor | CCR2 | ++ | NC | +++ | NC | |
| * NFκB | T-cells /MΦ/CCR6 | CCL20 | +++ | NC | ++ | NC/+ | |
| * DC & T-cells | CCL20 Receptor | CCR6 | + | NC | ↓ | NC | |
| IRF1/STAT1/NFκB | +Th1/CXCR10 | IP-10 | ++ | NC | +++ | ++ | |
| STAT6/ NFκB | +Th2/CCR4 | TARC | +++ | NC | NC | NC | |
| STAT6/NF-κB | Monocyte/Eos/CCR3 | Eotaxin 1 | ++ | +++ | NC | NC | |
|
Adhesion
Molecules |
STAT1/NF-κB/AP1 | Binds Integ β2/LFA-1 | ICAM-1 | NC/+ | NC | ++ | NC/+ |
| STAT6/ NF-κB | Binds Integ β1/VLA-4 | VCAM-1 | ++ | + | NC/+ | NC | |
|
Oxidative
Stress Inducers |
* NF-κB | +PGH2/TXA2 | COX2 | ++++ | NC | ++++ | NC |
| STAT1/NF-κB, Rac | +H2O2 | Nox2 | + | NC | ++ | NC/+ | |
| STAT1/NF-κB | NO production | iNOS | + | NC | ++ | NC/+ | |
| STAT6 | Polyamine+, -Arg | Arginase1 | + | NC | ↓ | NC | |
| Proteases | STAT1/NF-κB | IL-1b procession | Caspase 1 | NC/+ | NC | + | NC |
| NF-κB/APC | Mucosal degradation | MMP3 | ++++ | NC | +++ | NC | |
| STAT6/NF-κB | Mucosal degradation | ADAM8 | + | NC/↓ | NC | NC | |
|
Mucosal
Defense |
STAT3/Sp1 | Mucus barrier | Mucin1 | NC/+ | NC | NC | ++ |
| NF-κB /SP1 | Mucus barrier | Mucin5aC | +++++ | NC | ++ | NC/+ | |
| -NF-κB/CEBPβ | Repair/anti-apoptotic | TTF3 | ↓ | NC | NC | NC | |
| NF-κB | Anti-microbial | Defensin β2 | ++ | NC | NC/+ | ++ | |
| NF-κB | anti-apoptosis | BCL2 | + | NC | NC/+ | NC | |
| Control | None | GAPDH, β-Actin, S18 rRNA | NC | NC | NC | NC | |
Expression differences are shown in relation to colon biopsies from normal subjects and an arbitrary scale was set to represent those differences: NC = no change, NC/+ = notable change that did not reach statistical significance, + = significant change under 5-fold, ++ = 5-20 fold change, +++ = 20-100 fold change, ++++ = 100-1000-fold change, +++++ = more than 1000-fold change.
Designates that there is documented genetic association of the genes with IBD. The transcriptional regulation of genes is described here showing transcption factors that have been documented to modulate specific gene expression and is based on reference in the text. Also the function of each gene is briefly noted. Furthermore, other genes that have been quantified and did not show significant differences include: TLR4*, CARD 9*, IFN-γ receptor 1, IL-4Rα, IL-12rb, IL-17Ar, CCR4, CCR8, CXCR3, STAT1, STAT4, STAT6*, JAK1, JAK2*, JAK3, PTPN22*.
Antigen stimulation of TCR, GATAT3, NFAT, AP-1, chromatin remodeling (32).