Bacterial heat shock protein 60 may increase epithelial cell migration through activation of MAP kinases and inhibition of alpha6beta4 integrin expression.
Exogenous heat shock proteins may modify cell behavior of infected epithelium. The effect of heat shock protein 60 (hsp60) of Actinobacillus actinomycetemcomitans and Escherichia coli, and human recombinant hsp60 on migration of HaCaT skin keratinocytes was studied using the Boyden chamber assay. Hsp60 from different species increased cell migration by two- to fivefold and this effect was inhibited by ERK inhibitor PD 98059, p38 inhibitor SB 203580, and a function-blocking epidermal growth factor receptor (EGFR) antibody. Hsp60 reduced the expression of alpha6-integrin mRNA and its protein levels on the cell surface but had no effect on the expression of beta4, beta1, alpha1, alpha5 or alphav integrin subunits. Hsp60 also significantly inhibited cell adhesion to laminin-5, a ligand of alpha6beta4 integrin. These results suggest that exogenous hsp60 released from bacteria or inflammatory cells may promote epithelial cell migration through activation of EGFR and MAP kinases, and inhibition of alpha6beta4 integrin expression.
Zhang
Liangxuan
L
Department of Oral Biological and Medical Sciences, University of British Columbia, Vancouver, BC, Canada V6T 1Z3.
Koivisto
Leeni
L
Heino
Jyrki
J
Uitto
Veli-Jukka
VJ
D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D018834:Chaperonin 60 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D066246:ErbB Receptors / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D039161:Integrin alpha6beta4 / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology
D001426:Bacterial Proteins; D018834:Chaperonin 60; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D039161:Integrin alpha6beta4; D021122:Protein Subunits; D011725:Pyridines; D066246:ErbB Receptors; D020928:Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one