dc.description.abstract | Antibiotics without selectivity for acne treatment may destroy the beneficial microbes in the human microbiome that helps to fight Cutibacterium acnes (C. acnes), a bacterium associated with inflammatory acne vulgaris. Probiotic treatment by direct application of live Staphylococcus epidermidis (S. epidermidis) onto the open acne lesions may run the risk of bloodstream infections. Here, we fabricated the polysulfone microtube array membranes (PSF MTAM) to encapsulate probiotic S. epidermidis. We demonstrate that the application of the encapsulation of S. epidermidis in PSF MTAM enhanced the glycerol fermentation activities of S. epidermidis. To mimic the granulomatous type of acne inflammatory acne vulgaris, the ears of mice were injected intradermally with C. acnes to induce the secretion of macrophage inflammatory protein-2 (MIP-2), a murine counterpart of human interleukin (IL)-8. The C. acnes-injected mouse ears were covered with a PSF MTAM encapsulated with or without S. epidermidis in the presence of glycerol. The application of S. epidermidis-encapsulated PSF MTAM plus glycerol onto the C. acnes-injected mouse ears considerably reduced the growth of C. acnes and the production of MIP-2. Furthermore, no S. epidermidis leaked from PSF MTAM into mouse skin. The S. epidermidis-encapsulated PSF MTAM functions as a probiotic acne patch.
Stress is one of the major causal factors in the inhibition of hair growth. Here, we investigate the effect of sonic stress on the induction of skin inflammation and hair growth in inflammatory skin. Mice exposed to sonic stress created by ultrasonic rodent repellants significantly up-regulated mRNA expression of phosphodiesterase 4B (PDE4B), enhanced the production of 4-hydroxy-2-nonenals (4-HNE), a marker of reactive oxygen species (ROS) and a pro-inflammatory interleukin (IL)-6 cytokine, and stimulated substantial accumulation of macrophages in skin. The inflammatory skin elicited by sonic stress considerably impeded hair growth. Treatment of macrophage cells with recombinant IL-6 increased phosphorylated Bruton′s tyrosine kinase (p-BTK). The elevated 4-HNE and IL-6 as well as the restricted hair growth caused by sonic stress were subdued in PDE4B knockout mice. A probiotic Staphylococcus capitis (S. capitis) EHH strain-mediated glycerol fermentation to effectively suppress the inflammatory effect of sonic stress on the inhibition of hair growth. Experiments using siRNA knockdown validated that free fatty acid receptor 2 (FFAR2) mediated probiotic action of S. capitis EHH against sonic stress. The study elucidated a signaling pathway of PDE4B/4-HNE/IL-6 provoked by sonic stress and demonstrated a probiotic skin approach to mitigate the sonic stress-induced skin inflammation and retarded hair growth.
Membrane glycoprotein is the most abundant protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but its role in coronavirus disease 2019 (COVID-19) has not been fully characterized. The mice were intranasally inoculated with membrane glycoprotein substantially increased the interleukin (IL)-6, a hallmark of the cytokine storm, in bronchoalveolar lavage fluid (BALF), compared to mice inoculated with green fluorescent protein (GFP). The high level of IL-6 induced by membrane glycoprotein was significantly diminished in phosphodiesterase 4 (PDE4B) knockout mice, demonstrating the essential role of PDE4B in IL-6 signaling. Mycelium fermentation of Lactobacillus rhamnosus (L. rhamnosus) EH8 strain yielded butyric acid, which can down-regulate the PDE4B expression and IL-6 secretion in macrophages. Feeding mice with mycelia increased the relative abundance of commensal L. rhamnosus. Two-week supplementation of mice with L. rhamnosus plus mycelia considerably decreased membrane glycoprotein-induced PDE4B expression and IL-6 secretion. The probiotic activity of L. rhamnosus plus mycelia against membrane glycoprotein was abolished in mice treated with GLPG-0974, an antagonist of free fatty acid receptor 2 (Ffar2). Activation of Ffar2 in the gut-lung axis for down-regulation of the PDE4B-IL-6 signaling may provide targets for developing modalities, including probiotics for treating the cytokine storm in COVID-19. | en_US |