PMID- 30710344
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230201
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Linking)
VI  - 234
IP  - 9
DP  - 2019 Sep
TI  - Connexin 26 and 43 play a role in regulating proinflammatory events in the 
      epidermis.
PG  - 15594-15606
LID - 10.1002/jcp.28206 [doi]
AB  - Dysregulation of Connexin (CX) expression and function is associated with a range 
      of chronic inflammatory conditions including psoriasis and nonhealing wounds. To 
      mimic a proinflammatory environment, HaCaT cells, a model human keratinocyte cell 
      line, were challenged with 10 microg/ml peptidoglycan (PGN) isolated from 
      Staphylococcus aureus for 15 min to 24 hr in the presence or absence of CX 
      blockers and/or following CX26, CX43, PANX1 and TLR2 small interfering RNA 
      (siRNA) knockdown (KD). Expression levels of IL-6, IL-8, CX26, CX43, PANX1, TLR2 
      and Ki67 were assessed by quantitative real-time polymerase chain reaction, 
      western blot analysis and/or immunocytochemistry. Nuclear factor kappa beta (NF-kappabeta) 
      was blocked with BAY 11-7082, CX-channel function was determined by adenosine 
      5'-triphosphate (ATP) release assays. Enzyme-linked immunosorbent assay monitored 
      IL6 release following PGN challenge in the presence or absence of siRNA or 
      blockers of CX or purinergic signalling. Exposure to PGN induced IL-6, IL-8, CX26 
      and TLR2 gene expression but it did not influence CX43, PANX1 or Ki67 messenger 
      RNA expression levels. CX43 protein levels were reduced following 24 hr PGN 
      exposure. PGN-induced CX26 and IL-6 expression were also aborted by TLR2-KD and 
      inhibition of NF-kappabeta. ATP and IL-6 release were stimulated following 15 min and 
      1-24 hr challenge with PGN, respectively. Release of both agents was inhibited by 
      coincubation with CX-channel blockers, CX26-, CX43- and TLR2-KD. The IL-6 
      response was also reduced by purinergic blockers. CX-signalling plays a role in 
      the innate immune response in the epidermis. PGN is detected by TLR2, which via 
      NF-kappabeta, directly activates CX26 and IL-6 expression. CX43 and CX26 maintain 
      proinflammatory signalling by permitting ATP release, however, PANX1 does not 
      participate.
CI  - (c) 2019 Wiley Periodicals, Inc.
FAU - Garcia-Vega, Laura
AU  - Garcia-Vega L
AD  - Department of Biological and Biomedical Sciences, School of Health and Life 
      Sciences, Glasgow Caledonian University, Glasgow, Scotland, UK.
FAU - O'Shaughnessy, Erin M
AU  - O'Shaughnessy EM
AD  - Department of Biological and Biomedical Sciences, School of Health and Life 
      Sciences, Glasgow Caledonian University, Glasgow, Scotland, UK.
FAU - Jan, Afnan
AU  - Jan A
AD  - Department of Biological and Biomedical Sciences, School of Health and Life 
      Sciences, Glasgow Caledonian University, Glasgow, Scotland, UK.
FAU - Bartholomew, Chris
AU  - Bartholomew C
AD  - Department of Biological and Biomedical Sciences, School of Health and Life 
      Sciences, Glasgow Caledonian University, Glasgow, Scotland, UK.
FAU - Martin, Patricia E
AU  - Martin PE
AUID- ORCID: 0000-0003-0890-8059
AD  - Department of Biological and Biomedical Sciences, School of Health and Life 
      Sciences, Glasgow Caledonian University, Glasgow, Scotland, UK.
LA  - eng
GR  - ST3 15/Psoriasis Association/
GR  - PhD Schlolarship/Saudi Arabia Cultural Bureau/
GR  - Studentship/Glasgow Caledonian University/
PT  - Journal Article
DEP - 20190202
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
SB  - IM
OTO - NOTNLM
OT  - NF-kappabeta
OT  - Toll-like repector 2
OT  - connexin 26
OT  - connexin 43
OT  - epidermis
OT  - inflammation
OT  - intercellular signalling
OT  - pannexin 1
OT  - peptidoglycan
OT  - purinergic signalling
EDAT- 2019/02/03 06:00
MHDA- 2019/02/03 06:01
CRDT- 2019/02/03 06:00
PHST- 2019/01/15 00:00 [revised]
PHST- 2018/08/07 00:00 [received]
PHST- 2019/01/16 00:00 [accepted]
PHST- 2019/02/03 06:00 [pubmed]
PHST- 2019/02/03 06:01 [medline]
PHST- 2019/02/03 06:00 [entrez]
AID - 10.1002/jcp.28206 [doi]
PST - ppublish
SO  - J Cell Physiol. 2019 Sep;234(9):15594-15606. doi: 10.1002/jcp.28206. Epub 2019 
      Feb 2.