Tight junction transepithelial electrical resistance

The in vitro system we have been using to study the transepithelial transport is cultured Madin-Darby canine kidney (MDCK) epithelial cells (11). When cultured on microporous polycarbonate filters (Transwell, Costar, Cambridge, MA), MDCK cells will develop into monolayers mimicking the mucosal epithelium (11). When these cells reach confluence, tight junctions will be established between the cells, and free diffusion of solutes across the cell monolayer will be markedly inhibited. Tight junction formation can be monitored by measuring the transepithelial electrical resistance (TEER) across the cell monolayers. In Figure 1, MDCK cells were seeded at 2 X 104 cells per well in Transwells (0.4 p pore size) as described previously. TEER and 14C-sucrose transport were measured daily. To determine 14C-sucrose... 

Figure 15 An increase in transepithelial electrical resistance (TER) of MDCK cell monolayers with time in culture reflects the gradual formation of a continuous sheet of epithelia with restrictive tight junctions. [Redrawn from Cho et al. (1989) with permission from the publisher.]...

Baida MS, Whitney JA, Flores C, Gonzalez-Mariscal L, Cereijido M, and Matter K [1996] Functional dissociation of paracellular permeability and transepithelial electrical resistance and disruption of the apical-basolateral intramembrane diffusion barrier by the expression of a mutant tight junction membrane protein. J Cell Biol 134 1031-1049... 

The transepithelial electrical resistance measures predominantly the permeability of tight junctions for small ionic solutes. A partial disruption of tight junctions would not be detected by changes in permeability but by a drop in transepithelial resistance, which is reflected by an asymptotic relationship of... 

FIGURE 20.11 Effect of DHA-LPC itself on transepithelial electrical resistance (TEER) between the apical chamber and the basolateral chamber. When the TEER value decreases, it indicates that tight junctions between the epithelial cells are opened. 

In particular barrier systems such as the blood-brain barrier (BBB) are characterized by the so-called transepithelial electrical resistance (TEER). The TEER is considered an important measure of function and quality of tight junctions which are formed between endothelial cells making up the barrier. CThanges in TEER may indicate leakage due to toxic side effects of drugs or may be a desired effect of a drug that is to pass the BBB in order to treat a disease within the central nervous system. Also, TEER is routinely measured to establish proper function of a barrier system (BBB, gut) prior to the tests of drug permeability. 

Baida, M. S., Whitney, J. A., Flores, C., Gonzalez, S., Cereijido, M., and Matter, K. (1996). Functional dissociation of paracellular permeability and transepithelial electrical resistance and disruption of the apical-basolateral intramembrane diffusion barrier by expression of a mutant tight junction membrane protein. J. Cell Biol. 134, 1031-1049. Cereijido, M., Valdes, J., Shoshani, L., and Contreras, R. G. (1998). Role of tight junctions in establishing and maintaining cell polarity. Anna. Rev. Physiol. 60, 161-177. 

Transepithelial electrical resistance (TEER) measurements and transport smdies implied that CS/y-PGA NPs can be effective as an insulin carrier only in a limited area of the intestinal lumen where the pH values are close to the p/iTa of chitosan. So, a pH-responsive nanoparticle system was self-assembled by TMC and y-PGA for oral delivery of insulin. In contrast, TMC(40% Degree of Quatemisation) / y-PGA NPs may be a suitable carrier for transmucosal delivery of insulin within the entire intestinal tract. The loading efficiency and loading content of insulin in TMC/ y-PGA NPs were 73.8 2.9% and 23.5 2.1%, respectively. TMC/y-PGA NPs had superior stability in a broader pH range to CS/y-PGA NPs the in vitro release profiles of insulin from both test nanoparticles were significantly affected by their stability at distinct pH environments. TEER experiments showed that TMC/y-PGA NPs were able to open the tight junctions between Caco-2 cells, and this was further confirmed by confocal microscopy [66]. 

---