Induction of hyper-adhesion attenuates autoimmune-induced keratinocyte cell-cell detachment and processing of adhesion molecules via mechanisms that involve PKC.

Abstract

In confluent keratinocyte monolayers, desmosomal adhesion gradually becomes calcium-independent and this is associated with an increase in the strength of intercellular adhesion (hyper-adhesion). In this study, we investigated the functional and molecular significance of hyper-adhesion in a system challenged by autoimmune sera from patients with Pemphigus Vulgaris (PV), a disease primarily targeting desmosomal adhesion. The results show that keratinocytes with calcium-independent desmosomes are resistant to disruption of intercellular contacts (acantholysis) in experimental PV. Furthermore, both the desmosomal cadherins desmoglein (Dsg) 1 and Dsg3 and the adherens junction protein E-cadherin were decreased in confluent keratinocytes at Day 1, but not in hyper-adhesive cells (Day 6) after incubation with PV serum. Pharmacological induction of the hyper-adhesive state with the PKC inhibitor Go6976 reduced both the acantholysis rate and the processing of cell adhesion molecules induced by PV serum. When the establishment of the hyper-adhesive state was prevented by cell adhesion recognition (CAR) peptides that perturbed desmosomal interactions, Go6976 could still partially attenuate PV acantholysis. Taken together, these data demonstrate that keratinocyte hyper-adhesion decreases the morphological, functional and biochemical dys-cohesive effects of PV serum via mechanisms that involve, at least in part, the function of PKC. This suggests that reinforcing keratinocyte adhesion may be a promising way to inhibit the effects of this most debilitating disorder.

• Authors: Nicola Cirillo, Alessandro Lanza, Stephen S Prime
• Journal: Experimental cell research (Exp Cell Res) Vol. 316 Issue 4 Pg. 580-92 (Feb 15 2010) ISSN: 1090-2422 [Electronic] United States
• PMID: 19818770 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Crown Copyright 2009. Published by Elsevier Inc. All rights reserved.

Chemical References

• Cadherins
• Cell Adhesion Molecules
• DSG1 protein, human
• DSG3 protein, human
• Desmoglein 1
• Desmoglein 3
• Protein Kinase C

Topics

• Autoimmunity
• Blotting, Western
• Cadherins (metabolism)
• Cell Adhesion Molecules (metabolism)
• Cells, Cultured
• Desmoglein 1 (metabolism)
• Desmoglein 3 (metabolism)
• Down-Regulation
• Fluorescent Antibody Technique
• Glass (chemistry)
• Humans
• Keratinocytes (immunology)
• Models, Biological
• Pemphigus (blood, immunology)
• Protein Kinase C (metabolism)