Immunohistological pointers to a possible role for excessive cathelicidin (LL-37) expression by apocrine sweat glands in the pathogenesis of hidradenitis suppurativa/acne inversa

Br J Dermatol. 2012 May;166(5):1023-34. doi: 10.1111/j.1365-2133.2011.10765.x. Epub 2012 Apr 4.

Abstract

Background: The cause of follicular occlusion, a key early event in the pathogenesis of hidradenitis suppurativa (HS), also known as acne inversa, remains unknown.

Objectives: To identify changes, if any, in the antimicrobial peptide (AMP) and cytokine expression profile of HS affected human skin.

Methods: Quantitative immunohistomorphometry was used to compare the in situ protein expression of selected AMPs and cytokines in lesional HS skin from 18 patients with that in healthy skin (n = 12). The lesional skin from patients with HS was histologically subclassified based on the predominance of inflammation vs. scarring.

Results: Compared with healthy controls, significantly increased immunoreactivity for cathelicidin (LL-37) was noted in the apocrine sweat gland and distal outer root sheath (ORS) of the hair follicle (HF) epithelium in lesional HS skin. Immunoreactivity for LL-37, psoriasin, human β-defensin 3 (hBD3), α-melanocyte stimulating hormone (α-MSH), macrophage migration inhibitory factor (MIF), tumour necrosis factor (TNF)-α and interleukin (IL)-8 was significantly increased in HS epidermis. LL-37 and TNF-α immunoreactivity was also increased in the dermis of lesional HS skin. In contrast, lysozyme expression was decreased in the epidermis of lesional HS skin, while that of TNF-α and IL-8 was decreased in the proximal ORS of HFs in HS lesions. These differences were most pronounced in HS with predominant inflammation.

Conclusions: Our observations raise the question as to whether excessive secretion of AMPs by the skin, in particular by the apocrine sweat glands, distal HF epithelium, and epidermis, may attract inflammation and thus facilitate or promote HS development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antimicrobial Cationic Peptides / metabolism*
  • Case-Control Studies
  • Cathelicidins
  • Chemotactic Factors / metabolism
  • Dermis / metabolism
  • Epidermis / metabolism
  • Female
  • Hidradenitis Suppurativa / etiology*
  • Hidradenitis Suppurativa / metabolism
  • Humans
  • Immunohistochemistry
  • Interleukin-8 / metabolism
  • Male
  • Middle Aged
  • Muramidase / metabolism
  • S100 Calcium Binding Protein A7
  • S100 Proteins / metabolism
  • Sweat Glands / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation
  • Young Adult
  • alpha-MSH / metabolism
  • beta-Defensins / metabolism

Substances

  • Antimicrobial Cationic Peptides
  • Chemotactic Factors
  • DEFB103A protein, human
  • Interleukin-8
  • S100 Calcium Binding Protein A7
  • S100 Proteins
  • S100A7 protein, human
  • Tumor Necrosis Factor-alpha
  • beta-Defensins
  • macrophage migration enhancement factor
  • alpha-MSH
  • Muramidase
  • Cathelicidins