c-Jun N-terminal kinase is largely involved in the regulation of tricellular tight junctions via tricellulin in human pancreatic duct epithelial cells.
Tricellulin (TRIC) is a tight junction protein at tricellular contacts where three epithelial cells meet, and it is required for the maintenance of the epithelial barrier. To investigate whether TRIC is regulated via a c-Jun N-terminal kinase (JNK) pathway, human pancreatic HPAC cells, highly expressed at tricellular contacts, were exposed to various stimuli such as the JNK activators anisomycin and 12-O-tetradecanoylphorbol 13-acetate (TPA), and the proinflammatory cytokines IL-1β, TNFα, and IL-1α. TRIC expression and the barrier function were moderated by treatment with the JNK activator anisomycin, and suppressed not only by inhibitors of JNK and PKC but also by siRNAs of TRIC. TRIC expression was induced by treatment with the PKC activator TPA and proinflammatory cytokines IL-1β, TNFα, and IL-1α, whereas the changes were inhibited by a JNK inhibitor. Furthermore, in normal human pancreatic duct epithelial cells using hTERT-transfected primary cultured cells, the responses of TRIC expression to the various stimuli were similar to those in HPAC cells. TRIC expression in tricellular tight junctions is strongly regulated together with the barrier function via the JNK transduction pathway. These findings suggest that JNK may be involved in the regulation of tricellular tight junctions including TRIC expression and the barrier function during normal remodeling of epithelial cells, and prevent disruption of the epithelial barrier in inflammation and other disorders in pancreatic duct epithelial cells.
Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. ktakashi@sapmed.ac.jp
Takashi
T
Kojima
Jun
J
Fuchimoto
Hiroshi
H
Yamaguchi
Tatsuya
T
Ito
Akira
A
Takasawa
Takafumi
T
Ninomiya
Shin
S
Kikuchi
Noriko
N
Ogasawara
Tsuyoshi
T
Ohkuni
Tomoyuki
T
Masaki
Koichi
K
Hirata
Tetsuo
T
Himi
Norimasa
N
Sawada
D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D053582:Interleukin-1alpha / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D062794:MARVEL Domain Containing 2 Protein; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D062793:Occludin; D010183:Pancreatic Ducts / Q000187:drug effects / Q000201:enzymology*; D010539:Permeability; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D021381:Protein Transport; D034622:RNA Interference; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects / Q000201:enzymology*; D013997:Time Factors; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D020536:Enzyme Activators; D018836:Inflammation Mediators; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D062794:MARVEL Domain Containing 2 Protein; C516798:MARVELD2 protein, human; D008565:Membrane Proteins; D016328:NF-kappa B; C568985:OCLN protein, human; D062793:Occludin; D047428:Protein Kinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D011493:Protein Kinase C; D048031:JNK Mitogen-Activated Protein Kinases; C509186:TERT protein, human; D019098:Telomerase