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TnP and AHR-CYP1A1 Signaling Crosstalk in an Injury-Induced Zebrafish Inflammation Model.
Disner, Geonildo Rodrigo; Fernandes, Thales Alves de Melo; Nishiyama-Jr, Milton Yutaka; Lima, Carla; Wincent, Emma; Lopes-Ferreira, Monica.
Afiliação
  • Disner GR; Immunoregulation Unit, Laboratory of Applied Toxinology (CeTICS/FAPESP), Butantan Institute, São Paulo 05585-000, Brazil.
  • Fernandes TAM; Unit of System Toxicology, Institute of Environmental Medicine, Karolinska Institutet, 171 77 Solna, Sweden.
  • Nishiyama-Jr MY; Nucleus of Bioinformatics and Computational Biology, Laboratory of Applied Toxinology, Butantan Institute, São Paulo 05585-000, Brazil.
  • Lima C; Nucleus of Bioinformatics and Computational Biology, Laboratory of Applied Toxinology, Butantan Institute, São Paulo 05585-000, Brazil.
  • Wincent E; Immunoregulation Unit, Laboratory of Applied Toxinology (CeTICS/FAPESP), Butantan Institute, São Paulo 05585-000, Brazil.
  • Lopes-Ferreira M; Unit of System Toxicology, Institute of Environmental Medicine, Karolinska Institutet, 171 77 Solna, Sweden.
Pharmaceuticals (Basel) ; 17(9)2024 Aug 31.
Article em En | MEDLINE | ID: mdl-39338318
ABSTRACT
Aryl Hydrocarbon Receptor (AHR) signaling is crucial for regulating the biotransformation of xenobiotics and physiological processes like inflammation and immunity. Meanwhile, Thalassophryne nattereri Peptide (TnP), a promising anti-inflammatory candidate from toadfish venom, demonstrates therapeutic effects through immunomodulation. However, its influence on AHR signaling remains unexplored. This study aimed to elucidate TnP's molecular mechanisms on the AHR-cytochrome P450, family 1 (CYP1) pathway upon injury-induced inflammation in wild-type (WT) and Ahr2-knockdown (KD) zebrafish larvae through transcriptomic analysis and Cyp1a reporters. TnP, while unable to directly activate AHR, potentiated AHR activation by the high-affinity ligand 6-Formylindolo [3,2-b]carbazole (FICZ), implying a role as a CYP1A inhibitor, confirmed by in vitro studies. This interplay suggests TnP's ability to modulate the AHR-CYP1 complex, prompting investigations into its influence on biotransformation pathways and injury-induced inflammation. Here, the inflammation model alone resulted in a significant response on the transcriptome, with most differentially expressed genes (DEGs) being upregulated across the groups. Ahr2-KD resulted in an overall greater number of DEGs, as did treatment with the higher dose of TnP in both WT and KD embryos. Genes related to oxidative stress and inflammatory response were the most apparent under inflamed conditions for both WT and KD groups, e.g., Tnfrsf1a, Irf1b, and Mmp9. TnP, specifically, induces the expression of Hspa5, Hsp90aa1.2, Cxcr3.3, and Mpeg1.2. Overall, this study suggests an interplay between TnP and the AHR-CYP1 pathway, stressing the inflammatory modulation through AHR-dependent mechanisms. Altogether, these results may offer new avenues in novel therapeutic strategies, such as based on natural bioactive molecules, harnessing AHR modulation for targeted and sustained drug effects in inflammatory conditions.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Pharmaceuticals (Basel) Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Pharmaceuticals (Basel) Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça