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Differential susceptibility of C x26 mutations associated with epidermal dysplasias to peptidoglycan derived from Staphylococcus aureus and Staphylococcus epidermidis
Author(s) -
Donnelly Steven,
English Grant,
de ZwartStorm Eugene A.,
Lang Sue,
Steensel Maurice A. M.,
Martin Patricia E.
Publication year - 2012
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.1600-0625.2012.01521.x
Subject(s) - staphylococcus aureus , staphylococcus epidermidis , transfection , mutant , microbiology and biotechnology , peptidoglycan , biology , connexin , keratinocyte , cell culture , biochemistry , bacteria , intracellular , gap junction , gene , genetics
Mutations in Connexin26 ( C x26) give rise to a spectrum of dominantly inherited hyperproliferating skin disorders, the severest being keratitis–ichthyosis–deafness ( KID ) syndrome, an inflammatory skin disorder, with patients prone to opportunistic infections. We compared the effects of peptidoglycan ( PGN ) extracted from the skin commensal Staphylococcus epidermidis and the opportunistic pathogen Staphylococcus aureus on interleukin‐6 and connexin expression in H a C a T cells (a keratinocyte cell line) and connexin channel activity in H a C a T and H e L a (connexin deficient) cells transfected to express KID and non‐ KID Cx26 mutations. In both cell types, PGN from S. aureus induced hemichannel activity in cells expressing KID mutants as monitored by ATP release assays following 15‐min challenge, while that from S. epidermidis evoked a response in H e L a cells. In KID mutant expressing cells, ATP release was significantly higher than in cells transfected with wild‐type C x26. No ATP release was observed in non‐ KID mutant transfected cells or in the presence of carbenoxolone, a connexin channel blocker. PGN isolated from S. aureus but not S. epidermidis induced interleukin‐6 and C x26 expression in H a C a T cells following 6‐h challenge. Challenge by PGN from S. aureus evoked a greater interleukin‐6 response in cells expressing KID mutants than in cells expressing wt C x26 or non‐ KID mutants. This response returned to basal levels if acute KID hemichannel signalling was blocked prior to PGN challenge. Thus, KID mutants form channels that can be triggered by the pro‐inflammatory mediator PGN from opportunistic pathogens but not skin commensals, providing further insight into the genotype–phenotype relationship of C x26 disorders.