Regulation of epithelial–mesenchymal IL-1 signaling by PPARβ/δ is essential for skin homeostasis and wound healing

Abstract

Skin morphogenesis, maintenance, and healing after wounding require complex epithelial–mesenchymal interactions. In this study, we show that for skin homeostasis, interleukin-1 (IL-1) produced by keratinocytes activates peroxisome proliferator–activated receptor β/δ (PPARβ/δ) expression in underlying fibroblasts, which in turn inhibits the mitotic activity of keratinocytes via inhibition of the IL-1 signaling pathway. In fact, PPARβ/δ stimulates production of the secreted IL-1 receptor antagonist, which leads to an autocrine decrease in IL-1 signaling pathways and consequently decreases production of secreted mitogenic factors by the fibroblasts. This fibroblast PPARβ/δ regulation of the IL-1 signaling is required for proper wound healing and can regulate tumor as well as normal human keratinocyte cell proliferation. Together, these findings provide evidence for a novel homeostatic control of keratinocyte proliferation and differentiation mediated via PPARβ/δ regulation in dermal fibroblasts of IL-1 signaling. Given the ubiquitous expression of PPARβ/δ, other epithelial–mesenchymal interactions may also be regulated in a similar manner.

15-Hydroxyeicosatetraenoic Acid Is a Preferential Peroxisome Proliferator-Activated Receptor β/δ Agonist

“…In this context, it is also noteworthy that the agonistic effect of 15-HETE on PPAR␤/␦ was particular high is keratinocytes (HaCaT cells; Fig. 5B), where a growth-inhibitory role for PPAR␤/␦ is well established (Michalik et al, 2001;Kim et al, 2006;Burdick et al, 2007;Borland et al, 2008;Girroir et al, 2008;Chong et al, 2009). …”

Assessment of Antimicrobial Activity and Healing Potential of Mucous Secretion of Achatina fulica

“…Staphylococus epidermidis, on the other hand, has been related to high antibacterial resistance rates and nosocomial infections (Antunes et al, 2008). Therefore, since the healing is known to be affected by tissue bacteria concentrations higher than 10 5 microorganisms per gram (Chong et al, 2002), the use of dressing materials able to reduce content of these microorganisms in surgical dermal wounds, as performed in this study, might be useful to avoid wound infection and, therefore, favor wound healing (Ojiegbe et al).…”

TAK1 regulates SCF expression to modulate PKBα activity that protects keratinocytes from ROS-induced apoptosis

“…OTCs were performed as previously described. 11 Briefly, a fibroblast density of 1 Â 10 5 cells/ml of collagen was used to reconstruct OTCs. The air-exposed process was performed in a 371C incubator with 5% CO 2 and 70% humidity.…”

“…10 In the skin, these downstream mediators of TAK1 are important for the maintenance of epidermal homeostasis. 10,11 Perturbations to the JNK pathway have been implicated in epidermal hyperplasia leading to cancer development, while reduced NF-kB function is linked to epidermal squamous cell carcinoma. Blocking the NF-kB pathway through IKKb or IKKg inactivation also leads to severe skin inflammation.…”