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

Article Article scientifique Article 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 eng 2014-05-12 2014-05-12 author Ragupathy Sakthikumar 746248 author Esmaeili Farnaz 669025 author Paschoud Serge 594006 author Sublet Emmanuelle 514013 Section des sciences pharmaceutiques (FARMA) author Citi Sandra 0000-0002-6537-4818 116085 Département de biologie moléculaire et cellulaire (MOCEL) author Borchard Gerrit 0000-0001-6268-2586 635281 Section des sciences pharmaceutiques (FARMA) e29166 10.4161/tisb.29166 25101232 2168-8370 PMC4117686 http://www.tandfonline.com/doi/abs/10.4161/tisb.29166 <p>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 PKC? 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 ?, 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 ? activity.</p> Calu-3 Airway inflammation Barrier function Epithelial permeability Protein kinase C Tight junctions Toll-like receptor Dewey 615 Dewey 590 Dewey 570 43 Département de biologie moléculaire 161 46 Département de biologie cellulaire 165 31 Section des sciences pharmaceutiques 17 23 Institut de génétique et de génomique 0DH false 1441 Groupe Citi 879 Biopharmacie Tissue barriers 2 2 96d31baf-fb62-40c4-bd89-20818c8512f1 Article (Published version) Public Article-scientifique-from-unpaywall.pdf 3771423 application/pdf CC BY-NC-3.0 da1867699ef6d71c41f96b612d2a4c3d22bb50de8d01d49b3728628a1e72fc4a openAccess Faculté des sciences / Section de biologie / Département de biologie moléculaire Faculté des sciences / Section de biologie / Département de biologie cellulaire Faculté des sciences / Section des sciences pharmaceutiques Centres et instituts / Institut de génétique et de génomique

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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	Tissue barriers			2014	73	157

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Esmaeili, Farnaz