NOD2 signalling in hidradenitis suppurativa

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 beta-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 kappa B signalling.

Automated summary

The study found significantly elevated expression of NOD2 and related factors in Hidradenitis suppurativa (HS) skin samples and keratinocyte cultures. Moreover, there were correlations between NOD2 and other factors. The response of HS keratinocytes to stimuli differed from normal keratinocytes.