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• W2891891002 abstract "Background and Purpose Immunomodulatory tetracyclines are well-characterized drugs with a pharmacological potential beyond their antibiotic properties. Specifically, minocycline and doxycycline have shown beneficial effects in experimental colitis, although pro-inflammatory actions have also been described in macrophages. Therefore, we aimed to characterize the mechanism behind their effect in acute intestinal inflammation. Experimental Approach A comparative pharmacological study was initially used to elucidate the most relevant actions of immunomodulatory tetracyclines: doxycycline, minocycline and tigecycline; other antibiotic or immunomodulatory drugs were assessed in bone marrow-derived macrophages and in dextran sodium sulfate (DSS)-induced mouse colitis, where different barrier markers, inflammatory mediators, microRNAs, TLRs, and the gut microbiota composition were evaluated. The sequential immune events that mediate the intestinal anti-inflammatory effect of minocycline in DSS-colitis were then characterized. Key Results Novel immunomodulatory activity of tetracyclines was identifed; they potentiated the innate immune response and enhanced resolution of inflammation. This is also the first report describing the intestinal anti-inflammatory effect of tigecycline. A minor therapeutic benefit seems to derive from their antibiotic properties. Conversely, immunomodulatory tetracyclines potentiated macrophage cytokine release in vitro, and while improving mucosal recovery in colitic mice, they up-regulated Ccl2, miR-142, miR-375 and Tlr4. In particular, minocycline initially enhanced IL-1β, IL-6, IL-22, GM-CSF and IL-4 colonic production and monocyte recruitment to the intestine, subsequently increasing Ly6C−MHCII+ macrophages, Tregs and type 2 intestinal immune responses. Conclusions and Implications Immunomodulatory tetracyclines potentiate protective immune pathways leading to mucosal healing and resolution, representing a promising drug reposition strategy for the treatment of intestinal inflammation." @default.
• W2891891002 created "2018-09-27" @default.
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• W2891891002 date "2018-10-15" @default.
• W2891891002 modified "2023-10-18" @default.
• W2891891002 title "Immunomodulatory tetracyclines shape the intestinal inflammatory response inducing mucosal healing and resolution" @default.
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• W2891891002 doi "https://doi.org/10.1111/bph.14494" @default.
• W2891891002 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6240124" @default.
• W2891891002 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30184260" @default.
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