title: Long-term effects of tumor necrosis factor on LLC-PK1 transepithelial resistance.
abstract: Renal epithelial LLC-PK1 cell sheets incubated with tumor necrosis factor (TNF) undergo an acute, spontaneous, and rapidly reversible decrease in transepithelial resistance (TER). (Mullin et al., 1992). However, 24 to 72 h following TNF exposure, TER across the cell sheet increases 2-fold. This later effect of TNF is also reversible, albeit slowly. The TER of TNF-treated cell sheets then declines toward initial levels between 72 and 144 h following exposure to the cytokine. Whereas the long-term increase in TER following TNF exposure is not associated with a decreased transepithelial 14C-mannitol flux (size selectivity), the charge (anionic) selectivity of the LLC-PK1 tight junction is decreased. Basal-lateral (ouabain and bumetanide-insensitive) Rb+ and apical Na+-dependent alpha-methylglucoside (AMG) uptake into the cell are both reduced in cultures exposed to TNF 24 h earlier. Correspondingly, this long-term effect on TER is accompanied by a 30% decrease in short circuit current (iscc). Along with an observed increase in basal-lateral methylamino-isobutyric acid (MeAIB) influx into the cells, an increased incorporation of [3H]-thymidine into DNA indicates increased cell cycling after exposure to TNF. While the increase in cell cycling is not sustained for the duration of the elevation in TER, it does appear to initiate a sequence of events that lead to the sustained increase in TER. A decrease in the lateral intercellular space, observed between these epithelial cells after long-term TNF exposure, may be a mechanism for the elevated TER following from the mitogenesis and/or transport changes. This overall long-term tightening of an epithelium in response to TNF may function, in part, as a compensatory action of the epithelium to reestablish its effectiveness as a physiological barrier, following the acute effect of TNF.
authors.affiliation: Lankenau Medical Research Center, Wynnewood, PA 19096.
authors.forename: C W
authors.initials: CW
authors.lastname: Marano
authors.forename: K V
authors.initials: KV
authors.lastname: Laughlin
authors.forename: L M
authors.initials: LM
authors.lastname: Russo
authors.forename: A
authors.initials: A
authors.lastname: Peralta Soler
authors.forename: J M
authors.initials: JM
authors.lastname: Mullin
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D050260:Carbohydrate Metabolism; D004247:DNA / Q000096:biosynthesis; D004594:Electrophysiology; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D008353:Mannitol / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D010539:Permeability; D012413:Rubidium / Q000378:metabolism; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D000596:Amino Acids; D014409:Tumor Necrosis Factor-alpha; D008353:Mannitol; D010042:Ouabain; D004247:DNA; D012413:Rubidium