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. 2019 Aug 14;25(30):4125–4147. doi: 10.3748/wjg.v25.i30.4125

Table 3.

Current therapeutic approaches in inflammatory bowel diseases focused on intestinal epithelial cells

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.