Review
Copyright ©The Author(s) 2019.
World J Gastroenterol. Aug 14, 2019; 25(30): 4125-4147
Published online Aug 14, 2019. doi: 10.3748/wjg.v25.i30.4125
Table 3 Current therapeutic approaches in inflammatory bowel diseases focused on intestinal epithelial cells
Effects on IECsDrug typeDrug name/approachMechanism of actionRef.
Promotes physical barrier functions (by increasing proliferation and survival of IECs)Anti-IL-22BPInfliximab or adalimumabAnti-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 reducersTUDCA, PBAReduce apoptosis by increasing protein folding capacity of ER[112]
Human recombinant EGFEnemaPromotes proliferation and reduces apoptosis of ISCs[113,114]
Promotes physical barrier functions (by promoting expression and assembly of TJ proteins)Inhibitor of para-cellular permeabilityAT-1001Inhibits TJ disassembly by interfering with cytoskeletal rearrangement[115]
Vitamin DCalcitriol, vitamin D3 analogueInduces expression of TJ proteins and E-cadherin[117,179]
Sex hormoneEstradiol, diarylpropionitrile (estrogen receptor-β agonist)Induces expression of TJ proteins (occludin, junctional adhesion molecule-A)[118]
AMPK activatorMetforminInduces 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) agonistKAG-308, AGN205203Promotes mucus secretion and proliferation of goblet cells (Promotes proliferation and reduces apoptosis of IECs)[120,123,145,180,181]
Short chain fatty acidButyrateStimulates mucin production by HDAC inhibitor activity[121,124]
Recombinant anti-microbial peptideCathelicidinStimulates mucin production by MAPK dependent pathway[122,182]
Phosphatidylcholine (PC)LT-02Mucus 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 ligandImiquimodPromotes anti-microbial peptide (defensin) production in IECs[127]
ProbioticsEscherichia coli Nissle 1917Promotes 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-integrinEtrolizumab (anti-β7)Blocks the interaction between αEβ7 integrin on T cells with E-cadherin on IECs (Neutralizing antibody against integrin)[129]