Exp Clin Endocrinol Diabetes 2006; 114 - P12_155
DOI: 10.1055/s-2006-933040

Differential regulation of Toll-like receptor and CD14 pathways by retinoids and corticosteroids in human sebocytes

M Oeff 1, SR Bornstein 1, CC Zouboulis 2
  • 1TU Dresden, Medizinische Klinik III, Dresden, Germany
  • 2Charité – Universitätsmedizin Berlin, Abteilung für Dermatologie, Berlin, Germany

Objectives: Sebocytes are known to regulate androgen homeostasis within the skin, and may play a central role in the regulation of inflammation and immune functions following skin infection. We have currently shown human epithelial cells to induce and modulate inflammatory signals by Toll-like receptors (TLRs) and CD14 in acne. By this pathway the innate immunity is able to recognize microbial components, and induce cytokine /chemokine synthesis.

Methods: We examined the effects of retinoids, hydrocortisone (HC) and the microbial components lipopolysaccharide (LPS), and lipoteichoic acid (LTA) on TLR2, TLR4 and CD14 expression as well as on cytokine/chemokine expression in human SZ95 sebocytes by real-time quantitative PCR and ELISA.

Results: Human SZ95 sebocytes were found to constitutively express TLR2, TLR4, CD14, IL1α, IL1β, IL6 and IL8 that was augmented by exposure to components of gram-negative (LPS) and gram-positive (LTA) bacteria. Retinol (ROL) was the most active retinoid by slightly upregulating mRNA levels of TLR2, TLR4 and CD14, while isotretinoin (13cRA) and tretinoin (atRA) were practically inactive. Retinoids did not affect mRNA levels of IL-1α, IL-1β and IL-8 mRNA and their release. However, IL-6 mRNA levels and release was significantly reduced under retinoid treatment with 13cRA and atRA being more potent than ROL, indicating a selective, TLR-independent, anti-inflammatory effect of retinoids on SZ95 sebocytes. HC slightly upregulated TLR2 mRNA levels but markedly reduced TLR4 and CD14 mRNA levels. Furthermore, HC induced an overall reduction of cytokine/chemokine expression, a finding that undersigns its global antinflammatory activity.

Conclusion: We provide evidence that the pharmacological regulation of TLR and CD14 expression may provide a novel mechanism in the treatment of inflammatory acne lesions and other skin disorders associated with alterations in TLR regulation. Furthermore, there are several endocrine diseases which could be modulated by TLR agonists and antagonists.