NOD2 signalling in hidradenitis suppurativa

Abstract

Background: Hidradenitis suppurativa (HS) is associated with dysregulated immune responses including altered expression of cytokines, chemokines, and antimicrobial peptides and proteins (AMPs).

Aims: To evaluate the expression of nucleotide-binding oligomerization domain-containing (NOD)2 and related factors in HS skin samples and keratinocyte cultures.

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: 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: 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.