Table 3.
Effects on IECs | Drug type | Drug name/approach | Mechanism of action | Ref. |
Promotes physical barrier functions (by increasing proliferation and survival of IECs) | Anti-IL-22BP | Infliximab or adalimumab | Anti-TNF-α therapy may block the expression of IL-22BP, the endogenous inhibitor of IL-22 (IL-22 is known to promote IEC proliferation via STAT3 activation in ISCs) | [108-111] |
ER stress reducers | TUDCA, PBA | Reduce apoptosis by increasing protein folding capacity of ER | [112] | |
Human recombinant EGF | Enema | Promotes proliferation and reduces apoptosis of ISCs | [113,114] | |
Promotes physical barrier functions (by promoting expression and assembly of TJ proteins) | Inhibitor of para-cellular permeability | AT-1001 | Inhibits TJ disassembly by interfering with cytoskeletal rearrangement | [115] |
Vitamin D | Calcitriol, vitamin D3 analogue | Induces expression of TJ proteins and E-cadherin | [117,179] | |
Sex hormone | Estradiol, diarylpropionitrile (estrogen receptor-β agonist) | Induces expression of TJ proteins (occludin, junctional adhesion molecule-A) | [118] | |
AMPK activator | Metformin | Induces expression and assembly of TJ proteins via AMPK dependent pathway | [119] | |
Promotes biochemical barrier functions (by promoting mucus secretion or production) | PGE2 receptor (subtype EP4) agonist | KAG-308, AGN205203 | Promotes mucus secretion and proliferation of goblet cells (Promotes proliferation and reduces apoptosis of IECs) | [120,123,145,180,181] |
Short chain fatty acid | Butyrate | Stimulates mucin production by HDAC inhibitor activity | [121,124] | |
Recombinant anti-microbial peptide | Cathelicidin | Stimulates mucin production by MAPK dependent pathway | [122,182] | |
Phosphatidylcholine (PC) | LT-02 | Mucus component supplement for UC patients who have reduced PC in rectal mucus | [125,126,183] | |
Promotes biochemical barrier functions (by promoting anti-microbial peptide secretion or production) | TLR7 ligand | Imiquimod | Promotes anti-microbial peptide (defensin) production in IECs | [127] |
Probiotics | Escherichia coli Nissle 1917 | Promotes anti-microbial peptide (defensin) production in IECs by NF-kB activation | [128,184] | |
Corrects innate immune barrier dysfunctions (by inhibiting the retention of T cells in inflamed site) | Gut specific anti-integrin | Etrolizumab (anti-β7) | Blocks the interaction between αEβ7 integrin on T cells with E-cadherin on IECs (Neutralizing antibody against integrin) | [129] |
IECs: Intestinal epithelial cells; IL-22BP: Interleukin-22 binding protein; STAT3: Signal transducer and activator of transcription 3; ISCs: Intestinal stem cells; ER: Endoplasmic reticulum; TUDCA: Tauroursodeoxycholate; PBA: 4-phenyl butyrate; EGF: Epidermal growth factor; TJ: Tight junction; AMPK: Adenosine monophosphate-activated protein kinase; PGE2: Prostaglandin E2; EP4: Prostaglandin E2 receptor 4; HDAC: Histone deacetylase; MAPK: Mitogen activated protein kinase; UC: Ulcerative colitis; TLR7: Toll-like receptor 7; NF-kB: Nuclear factor kappa B; IECs: Intestinal epithelial cells.