NOD2 signalling in hidradenitis suppurativa.
Journal
Clinical and experimental dermatology
ISSN: 1365-2230
Titre abrégé: Clin Exp Dermatol
Pays: England
ID NLM: 7606847
Informations de publication
Date de publication:
Dec 2021
Dec 2021
Historique:
revised:
29
04
2021
received:
17
02
2021
accepted:
27
05
2021
pubmed:
1
6
2021
medline:
4
2
2022
entrez:
31
5
2021
Statut:
ppublish
Résumé
Hidradenitis suppurativa (HS) is associated with dysregulated immune responses including altered expression of cytokines, chemokines, and antimicrobial peptides and proteins (AMPs). To evaluate the expression of nucleotide-binding oligomerization domain-containing (NOD)2 and related factors in HS skin samples and keratinocyte cultures. We performed real-time PCR for NOD2, receptor-interacting serine/threonine-protein kinase (RIP)2, cyclic amine resistance locus (CARL), skin-derived antileukoproteinase (SKALP)/elafin, human β-defensin (hBD)2, LL37, psoriasin and RNAse7 in lesional and nonlesional skin of 19 patients with HS and in keratinocyte cultures [unstimulated, muramyl dipeptide (MDP)-stimulated or Pam2CSK4 (Pam2)-stimulated] from and nonlesional skin. We observed significantly elevated mRNA expression for NOD2 (P < 0.01), hBD2 (P = 0.02), RNase7 (P < 0.001), psoriasin (P < 0.01) and SKALP/elafin (P = 0.02) in lesional compared with nonlesional skin. We found a significant correlation between NOD2 mRNA and hBD2 (r = 46; P = 0.04), psoriasin (r = 0.67; P < 0.01) and SKALP/elafin (r = 0.65; P < 0.01). In unstimulated, Pam2-stimulated and MDP-stimulated normal keratinocytes, NOD2, RIP2, CARL and SKALP/elafin expression significantly (P < 0.05) increased from 6 to 48 h, whereas in unstimulated, Pam2-stimulated and MDP-stimulated HS keratinocytes, RIP2, CARL and SKALP/elafin expression significantly (P < 0.05) declined from 6 to 48 h. mRNA expression of NOD2 (unstimulated, Pam2-stimulated, MDP-stimulated), CARL (unstimulated, Pam2-stimulated, MDP-stimulated) and SKALP/elafin (unstimulated, Pam2-stimulated) at 6 h was significantly increased in HS compared with normal keratinocytes. We have shown for the first time that NOD2 signalling is activated in HS and might contribute to the pathogenesis via induction of AMPs and activation of other pathways such as nuclear factor κB signalling.
Sections du résumé
BACKGROUND
BACKGROUND
Hidradenitis suppurativa (HS) is associated with dysregulated immune responses including altered expression of cytokines, chemokines, and antimicrobial peptides and proteins (AMPs).
AIMS
OBJECTIVE
To evaluate the expression of nucleotide-binding oligomerization domain-containing (NOD)2 and related factors in HS skin samples and keratinocyte cultures.
METHODS
METHODS
We performed real-time PCR for NOD2, receptor-interacting serine/threonine-protein kinase (RIP)2, cyclic amine resistance locus (CARL), skin-derived antileukoproteinase (SKALP)/elafin, human β-defensin (hBD)2, LL37, psoriasin and RNAse7 in lesional and nonlesional skin of 19 patients with HS and in keratinocyte cultures [unstimulated, muramyl dipeptide (MDP)-stimulated or Pam2CSK4 (Pam2)-stimulated] from and nonlesional skin.
RESULTS
RESULTS
We observed significantly elevated mRNA expression for NOD2 (P < 0.01), hBD2 (P = 0.02), RNase7 (P < 0.001), psoriasin (P < 0.01) and SKALP/elafin (P = 0.02) in lesional compared with nonlesional skin. We found a significant correlation between NOD2 mRNA and hBD2 (r = 46; P = 0.04), psoriasin (r = 0.67; P < 0.01) and SKALP/elafin (r = 0.65; P < 0.01). In unstimulated, Pam2-stimulated and MDP-stimulated normal keratinocytes, NOD2, RIP2, CARL and SKALP/elafin expression significantly (P < 0.05) increased from 6 to 48 h, whereas in unstimulated, Pam2-stimulated and MDP-stimulated HS keratinocytes, RIP2, CARL and SKALP/elafin expression significantly (P < 0.05) declined from 6 to 48 h. mRNA expression of NOD2 (unstimulated, Pam2-stimulated, MDP-stimulated), CARL (unstimulated, Pam2-stimulated, MDP-stimulated) and SKALP/elafin (unstimulated, Pam2-stimulated) at 6 h was significantly increased in HS compared with normal keratinocytes.
CONCLUSION
CONCLUSIONS
We have shown for the first time that NOD2 signalling is activated in HS and might contribute to the pathogenesis via induction of AMPs and activation of other pathways such as nuclear factor κB signalling.
Substances chimiques
NOD2 protein, human
0
Nod2 Signaling Adaptor Protein
0
RNA, Messenger
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1488-1494Informations de copyright
© 2021 The Authors. Clinical and Experimental Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.
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