Inflammatory skin diseases, including atopic dermatitis (AD) and psoriasis, are increasing in populations worldwide. The treatment of patients with AD and other forms of skin inflammation is mainly based on the use of topical corticosteroids or calcineurin inhibitors, which can cause significant side effects with long-term use. Therefore, there is a great need for the development of more effective and less toxic anti-inflammatory agents suitable for the treatment of chronic skin lesions. Here, we screened a number of strains from the ASIB 505 terrestrial algae collection and identified a green algae Chromochloris zofingiensis with pronounced anti-inflammatory properties. We found that a crude nonpolar extract of C. zofingiensis (ID name NAE_2022C), grown upon nitrogen deprivation, acts as a bioactive substance by inhibiting TNFR/NF-κB responses in human skin keratinocyte HaCaT cells. We also found that NAE_2022C suppressed the secretion of pro-inflammatory cytokine tumor necrosis factor α (TNFα) and several Th1- and Th2-related chemokines in a reconstituted human epidermis. The TNFR/NF-κB pathway analysis showed multiple inhibitory effects at different levels and disclosed a direct targeting of IKKβ by the extract. Bioassay-guided fractionation followed by high-resolution mass spectrometry detected diacylglyceryl-trimethylhomoserine (DGTS), Lyso-DGTS (LDGTS), 5-phenylvaleric acid, theophylline and oleamide as leading metabolites in the active fraction of NAE_2022C. Further analysis identified betaine lipid DGTS (32:0) as one of the active compounds responsible for the NAE_2022C-mediated NF-κB suppression. Overall, this study presents an approach for the isolation, screening, and identification of anti-inflammatory secondary metabolites produced by soil algae.
He is a member of the editorial board of the Invertebrate Survival Journal and the European Journal of Zoology, and is a founding member of the Italian Association of Developmental and Comparative Immunobiology (IADCI). His main research interests are the evolution of innate immunity and the study of the cellular and molecular basis of immune responses in marine invertebrates, with particular reference to the role of hemocytes/coelomocytes in immune defense and, more generally, in the stress response. Most of his studies were carried out using the colonial ascidian Botryllus schlosseri as a model organism. His interest in stem cells is directly related to their role in hematopoiesis, as they assure the continuous renewal of the circulating immunocytes of marine invertebrates. He is the chair of the COST Action 16203 MARISTEM "Stem cells of marine/aquatic invertebrates: from basic research to innovative applications" that supported the publication of this book. He is the author or co-author of more than 130 peer-reviewed publications in scientific journals, co-editor of scientific books, including "Lessons in immunity: from singlecell organisms to mammals" (Elsevier, 2016), and guest editor of Special Issues, including: "Ancient immunity. phylogenetic emergence of recognition-defence mechanisms" (Biology (Basel), 2020-2021).Baruch (Buki) Rinkevich has been a professor and senior scientist at the
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