Previously, we proposed the hypothesis that similarities in the inflammatory response observed in acne vulgaris and degenerative disc disease (DDD), especially the central role of interleukin (IL)-1β, may be further evidence of the role of the anaerobic bacterium Cutibacterium (previously Propionibacterium) acnes in the underlying aetiology of disc degeneration. To investigate this, we examined the upregulation of IL-1β, and other known IL-1β-induced inflammatory markers and neurotrophic factors, from nucleus-pulposus-derived disc cells infected in vitro with C. acnes for up to 48 h. Upon infection, significant upregulation of IL-1β, alongside IL-6, IL-8, chemokine (C-C motif) ligand 3 (CCL3), chemokine (C-C motif) ligand 4 (CCL4), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), was observed with cells isolated from the degenerative discs of eight patients versus non-infected controls. Expression levels did, however, depend on gene target, multiplicity and period of infection and, notably, donor response. Pre-treatment of cells with clindamycin prior to infection significantly reduced the production of pro-inflammatory mediators. This study confirms that C. acnes can stimulate the expression of IL-1β and other host molecules previously associated with pathological changes in disc tissue, including neo-innervation. While still controversial, the role of C. acnes in DDD remains biologically credible, and its ability to cause disease likely reflects a combination of factors, particularly individualised response to infection.
One of the most important features of embryonic cells is their resistence to xenobiotics, which provides a natural protection for embryos against these potentially harmful molecules. In this way, embryo cells resemble cancer cells and thus understanding the basis of this phenomenon may contribute to overcoming the multi-drug-resistance (MDR) of some tumours. Peroxisome proliferator-activated receptors (PPARs) are steroid nuclear receptors that regulate diverse biological processes such as lipid and carbohydrate metabolism, development, differentiation, apoptosis, neoplastic transformation, inflammation and regeneration of tissues. Recently it has been found that they may also regulate the expression of some MDR proteins. In this article we summarise the main known relationships between some MDR pumps and three isoforms of PPAR receptors (PPAR-alpha, PPAR-beta/delta, PPAR-gamma). We hypothesize that regulation of MDR proteins by PPAR ligands in embryos could lead to the improvement of cancer treatment.