4.7 Article

Luteolin promotes pathogen resistance in Caenorhabditis elegans via DAF-2/DAF-16 insulin-like signaling pathway

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INTERNATIONAL IMMUNOPHARMACOLOGY
卷 115, 期 -, 页码 -

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ELSEVIER
DOI: 10.1016/j.intimp.2023.109679

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Luteolin; Innate immunity; DAF-2; DAF-16 insulin-like signaling pathway; C; elegans

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The DAF-2/DAF-16 insulin-like signaling pathway regulates various aspects of organismal physiology and is conserved throughout evolution. Luteolin, a flavone found in many plants and vegetables, has been shown to have anti-tumor, antioxidant, and neuroprotective effects. This study found that luteolin increased resistance to both Gram-negative and Gram-positive pathogens in a dose-dependent manner and promoted host immune response. Furthermore, it was discovered that luteolin activated the DAF-16/FOXO transcription factor and promoted innate immunity through the DAF-2/DAF-16 insulin-like signaling pathway.
The DAF-2/DAF-16 insulin-like signaling pathway was an evolutionarily conserved pathway, which regulated many aspects of organismal physiology, such as pathogen resistance, metabolism, stress response, longevity. Luteolin, a flavone contained in many medical plants and in vegetables, had been shown to exhibit activities such as anti-tumor, anti-oxidant and neuroprotective effects. However, whether the Luteolin influenced the immune response and the underlying molecular mechanisms remained obscure. We found that Luteolin increased resis-tance to not only the Gram-negative pathogens Pseudomonas aeruginosa and Salmonella enterica but also the Gram-positive pathogens Enterococcus faecalis and Staphylococcus aureus in dose dependent manner. Meanwhile, Luteolin promoted host immune response via inhibiting the growth of pathogenic bacteria. Through the genetic screening in C. elegans, we found that Luteolin promoted innate immunity via DAF-2/DAF-16 insulin-like signaling pathway rather than p38 MAPK pathway and SKN-1. Furthermore, Luteolin activated the DAF-16/ FOXO transcription factor for innate immune response. Our work suggested that Luteolin had the potential of improving the patients with pathogen infection.

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