Psoriatic patients have altered microbiota, both in the intestine and on the skin. It is not clear, however, whether this is a cause or consequence of the disease. In this study, using an experimental mouse model of psoriasis induced by imiquimod (IMQ), we show that oral treatment with a broad spectrum of antibiotics (MIX) or metronidazole (MET) alone mitigates the severity of skin inflammation through downregulation of Th17 immune response in conventional mice. Since some antibiotics, including MET, can influence immune system reactivity, we also evaluated the effect of MIX in the same model under germ-free (GF) conditions. GF mice treated with MET did not show milder signs of imiquimod-induced skin inflammation (IISI) which supports the conclusion that the therapeutic effect is mediated by changes in microbiota composition. Moreover, compared to controls, mice treated with MIX had a significantly higher abundance of the genus Lactobacillus in the intestine and on the skin. Mice treated with MET had a significantly higher abundance of the genera Bifidobacterium and Enterococcus both on the skin and in the intestine and of Parabacteroides distasonis in the intestine. Additionally, GF mice and mice monocolonized with either Lactobacillus plantarum or segmented filamentous bacteria (SFB) were more resistant to IISI than conventional mice. Interestingly, compared to GF mice, IMQ induced a higher degree of systemic Th17 activation in mice monocolonized with SFB but not with L. plantarum. The present findings provide evidence that intestinal and skin microbiota directly regulates IISI and emphasizes the importance of microbiota in the pathogenesis of psoriasis.

• Keywords
• animal model, antibiotics, germ-free, imiquimod, intestine, microbiota, psoriasis, skin,
• Publication type
• Journal Article MeSH

Nutritional factors which exhibit antioxidant properties, such as those contained in green plants, may be protective against cancer. Chlorophyll and other tetrapyrrolic compounds which are structurally related to heme and bilirubin (a bile pigment with antioxidant activity) are among those molecules which are purportedly responsible for these effects. Therefore, the aim of our study was to assess both the antiproliferative and antioxidative effects of chlorophylls (chlorophyll a/b, chlorophyllin, and pheophytin a) in experimental pancreatic cancer. Chlorophylls have been shown to produce antiproliferative effects in pancreatic cancer cell lines (PaTu-8902, MiaPaCa-2, and BxPC-3) in a dose-dependent manner (10-125 μmol/L). Chlorophylls also have been observed to inhibit heme oxygenase (HMOX) mRNA expression and HMOX enzymatic activity, substantially affecting the redox environment of pancreatic cancer cells, including the production of mitochondrial/whole-cell reactive oxygen species, and alter the ratio of reduced-to-oxidized glutathione. Importantly, chlorophyll-mediated suppression of pancreatic cancer cell viability has been replicated in in vivo experiments, where the administration of chlorophyll a resulted in the significant reduction of pancreatic tumor size in xenotransplanted nude mice. In conclusion, this data suggests that chlorophyll-mediated changes on the redox status of pancreatic cancer cells might be responsible for their antiproliferative and anticancer effects and thus contribute to the decreased incidence of cancer among individuals who consume green vegetables.

• MeSH
• Antioxidants metabolism   MeSH
• Chlorophyll pharmacology   MeSH
• Extracellular Signal-Regulated MAP Kinases metabolism   MeSH
• Pheophytins metabolism   MeSH
• Glutathione metabolism   MeSH
• Glutathione Disulfide metabolism   MeSH
• Heme Oxygenase (Decyclizing) metabolism   MeSH
• Real-Time Polymerase Chain Reaction MeSH
• Humans MeSH
• Mitochondria drug effects   metabolism   MeSH
• Cell Line, Tumor MeSH
• Pancreatic Neoplasms metabolism   MeSH
• Oxidation-Reduction drug effects   MeSH
• Hydrogen Peroxide metabolism   MeSH
• Antineoplastic Agents pharmacology   MeSH
• Superoxides metabolism   MeSH
• Synechocystis chemistry   MeSH
• Cell Survival drug effects   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Antioxidants MeSH
• Chlorophyll MeSH
• Extracellular Signal-Regulated MAP Kinases MeSH
• Pheophytins MeSH
• Glutathione MeSH
• Glutathione Disulfide MeSH
• Heme Oxygenase (Decyclizing) MeSH
• Hydrogen Peroxide MeSH
• pheophytin a MeSH Browser
• Antineoplastic Agents MeSH
• Superoxides MeSH

Psoriasis is a chronic inflammatory skin disease in which Th17 cells play a crucial role. Since indigenous gut microbiota influences the development and reactivity of immune cells, we analyzed the link among microbiota, T cells and the formation of psoriatic lesions in the imiquimod-induced murine model of psoriasis. To explore the role of microbiota, we induced skin inflammation in germ-free (GF), broad-spectrum antibiotic (ATB)-treated or conventional (CV) BALB/c and C57BL/6 mice. We found that both mice reared in GF conditions for several generations and CV mice treated with ATB were more resistant to imiquimod-induced skin inflammation than CV mice. The ATB treatment dramatically changed the diversity of gut bacteria, which remained stable after subsequent imiquimod application; ATB treatment resulted in a substantial increase in the order Lactobacillales and a significant decrease in Coriobacteriales and Clostridiales. Moreover, as compared to CV mice, imiquimod induced a lower degree of local and systemic Th17 activation in both GF and ATB-treated mice. These findings suggest that gut microbiota control imiquimod-induced skin inflammation by altering the T cell response.

• MeSH
• Actinobacteria drug effects   physiology   MeSH
• Lymphocyte Activation drug effects   MeSH
• Aminoquinolines pharmacology   MeSH
• Anti-Bacterial Agents pharmacology   MeSH
• Th17 Cells drug effects   immunology   microbiology   MeSH
• Clostridiales drug effects   physiology   MeSH
• Species Specificity MeSH
• Gene Expression MeSH
• Germ-Free Life MeSH
• Imiquimod MeSH
• Interleukin-17 genetics   immunology   MeSH
• Nuclear Receptor Subfamily 1, Group F, Member 3 genetics   immunology   MeSH
• Skin drug effects   immunology   microbiology   pathology   MeSH
• Lactobacillales drug effects   physiology   MeSH
• Humans MeSH
• Disease Models, Animal MeSH
• Mice, Inbred BALB C MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Psoriasis chemically induced   immunology   microbiology   pathology   MeSH
• Receptors, Antigen, T-Cell, gamma-delta genetics   immunology   MeSH
• Gastrointestinal Microbiome drug effects   physiology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Aminoquinolines MeSH
• Anti-Bacterial Agents MeSH
• Imiquimod MeSH
• Interleukin-17 MeSH
• Nuclear Receptor Subfamily 1, Group F, Member 3 MeSH
• Receptors, Antigen, T-Cell, gamma-delta MeSH
• Rorc protein, mouse MeSH Browser