Enhancement of tight junctional barrier function by micronutrients: compound-specific effects on permeability and claudin composition.
Amid an increasing number of reports in the literature concerning epithelial barrier enhancement by various nutrient compounds, there has never been a study performing side-by-side comparisons of these agents in a single epithelial model. We compare five nutrient compounds (previously reported in various epithelial models to enhance barrier function) regarding their ability to increase transepithelial electrical resistance (R(t)) and decrease transepithelial mannitol permeability (J(m)) across LLC-PK₁ renal epithelial cell layers. The effects of these nutrients on the abundance of various tight junctional proteins are also compared. In the overall group of nutrients tested--zinc, indole, quercetin, butyrate and nicotine--only nicotine failed to improve barrier function by either parameter. Nicotine also was without effect on tight junctional proteins. Quercetin simultaneously increased R(t) and decreased J(m). Zinc, butyrate and indole only exhibited statistically significant enhancement of R(t). Each of these four effective nutrient compounds had unique patterns of effects on the panel of tight junctional proteins studied. No two compounds produced the same pattern of effects. This unique pattern of effects on tight junctional complex composition by each compound establishes the chance for additive or even synergistic improvement of barrier function by combinations of compounds. A synergistic effect of the combination of quercetin and zinc on R(t) is shown.
Lankenau Institute for Medical Research, Wynnewood, Pennsylvania, United States of America.
Joanna
J
Mercado
Mary Carmen
MC
Valenzano
Cameron
C
Jeffers
Jason
J
Sedlak
Marina K
MK
Cugliari
Eleni
E
Papanikolaou
Jacob
J
Clouse
Jingya
J
Miao
Nina E
NE
Wertan
James M
JM
Mullin
D000818:Animals; D001692:Biological Transport; D002087:Butyrates / Q000494:pharmacology; D002460:Cell Line; D002463:Cell Membrane Permeability; D057167:Claudins / Q000378:metabolism*; D017097:Electric Impedance; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D007211:Indoles / Q000494:pharmacology; D008353:Mannitol / Q000378:metabolism; D018977:Micronutrients / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology; D011794:Quercetin / Q000494:pharmacology; D034421:Sus scrofa; D062725:Tight Junction Proteins / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects / Q000502:physiology*; D015032:Zinc / Q000494:pharmacology*
D002087:Butyrates; D057167:Claudins; D007211:Indoles; D018977:Micronutrients; D062725:Tight Junction Proteins; D008353:Mannitol; D009538:Nicotine; C030374:indole; D011794:Quercetin; D015032:Zinc