Toll-like receptor 2 regulates the barrier function of human bronchial epithelial monolayers through atypical protein kinase C zeta, and an increase in expression of claudin-1
| Autor: | Sandra Citi, Sakthikumar Ragupathy, Gerrit Borchard, Serge Paschoud, Farnaz Esmaeili, Emmanuelle Sublet |
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| Rok vydání: | 2013 |
| Předmět: |
Histology
tight junctions Calu-3 epithelial permeability Biology airway inflammation Occludin Biochemistry 03 medical and health sciences 0302 clinical medicine Receptor Claudin Barrier function Protein kinase C 030304 developmental biology 0303 health sciences Tight junction Cell Biology Cell biology 030220 oncology & carcinogenesis Paracellular transport Phosphorylation toll-like receptor barrier function Research Paper protein kinase C |
| Zdroj: | Tissue Barriers Tissue barriers |
| ISSN: | 2168-8362 |
| Popis: | We investigated the role of Toll-like receptor (TLR) 2 in maintaining the integrity of the airway epithelial barrier using the human bronchial epithelial cell line Calu-3. Activation of TLR2 by its ligands, Pam3CysSK4 and Peptidoglycan showed a concentration dependent increase in epithelial barrier function, as measured by transepithelial electrical resistance (TEER). This was confirmed by a decrease in paracellular flux of fluorescein sodium. This TLR2 induced increase in TEER was significantly reduced by pretreatment with polyclonal anti-human TLR2-neutralizing antibody. TLR2 stimulation in Calu-3 cell monolayers resulted in an increased expression of the tight junction proteins claudin-1 and ZO-1, and a decreased expression of occludin, at both the mRNA and protein levels. A pseudosubstrate inhibitor to PKCζ significantly prevented the TLR2 mediated increase in barrier function. It also prevented the increase in claudin-1 in a concentration dependent manner up to 1 µM. TLR2 stimulation led to an increase in phosphorylation of atypical PKC ζ, which was prevented by the pseudosubstrate inhibitor in a concentration dependent manner. Taken together, our observations support a model whereby increased tight junction barrier function induced by activation of TLR2 occurs through increased expression of claudin-1, and through modulation of PKC ζ activity. |
| Databáze: | OpenAIRE |
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