title: The reversible increase in tight junction permeability induced by capsaicin is mediated via cofilin-actin cytoskeletal dynamics and decreased level of occludin.
abstract: Previous results demonstrated that capsaicin induces the reversible tight junctions (TJ) opening via cofilin activation. The present study investigated the mechanisms underlying the reversible TJ opening and compared the effect to the irreversible opening induced by actin inhibitors. Capsaicin treatment induced the F-actin alteration unique to capsaicin compared to actin-interacting agents such as latrunculin A, which opens TJ irreversibly. Along with TJ opening, capsaicin decreased the level of F-actin at bicellular junctions but increased it at tricellular junctions accompanied with its concentration on the apical side of the lateral membrane. No change in TJ protein localization was observed upon exposure to capsaicin, but the amount of occludin was decreased significantly. In addition, cosedimentation analyses suggested a decrease in the interactions forming TJ, thereby weakening TJ tightness. Introduction of cofilin, LIMK and occludin into the cell monolayers confirmed their contribution to the transepithelial electrical resistance decrease. Finally, exposure of monolayers to capsaicin augmented the paracellular passage of both charged and uncharged compounds, as well as of insulin, indicating that capsaicin can be employed to modulate epithelial permeability. Our results demonstrate that capsaicin induces TJ opening through a unique mechanism, and suggest that it is a new type of paracellular permeability enhancer.
authors.affiliation: Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Shiobara
authors.forename: Takeo
authors.initials: T
authors.lastname: Usui
authors.forename: Junkyu
authors.initials: J
authors.lastname: Han
authors.forename: Hiroko
authors.initials: H
authors.lastname: Isoda
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nagumo
mesh_terms: D051339:Actin Depolymerizing Factors / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects*; D003599:Cytoskeleton / Q000378:metabolism*; D004285:Dogs; D006801:Humans; D061985:Madin Darby Canine Kidney Cells; D062793:Occludin / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D015398:Signal Transduction / Q000187:drug effects; D062725:Tight Junction Proteins / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects* / Q000378:metabolism
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D062793:Occludin; D062725:Tight Junction Proteins; D002211:Capsaicin