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A LINK BETWEEN VITAMIN B6 AND H2S IN OXIDATIVE STRESS-INDUCED SKIN INFLAMMATION
Autores:
FRANCISCO JUAN MARTINEZ NAVARRO
,
FRANCISCO JAVIER MARTÍNEZ MORCILLO
, RAÚL CORBALÁN VÉLEZ, Mª TERESA MARTÍNEZ MENCHÓN,
JOSE MESEGUER PEÑALVER
,
DIANA GARCIA MORENO
,
VICTORIANO MULERO MÉNDEZ
,
Grupos de investigación:
[GI/IMIB/C060/2011] Inmunidad, inflamación y cáncer
[GI/IMIB/C003/2011] Cirugía digestiva, endocrina y trasplante de órganos abdominales
Comunicación:
Antecedentes:
Psoriasis is a skin inflammatory disorder that affects 1-3 % of the human populations. Although several therapies based in the neutralization of proinflammatory cytokines have been used with relative success, they have important side effects. Therefore, additional treatments are required. Using a metabolomic approach in a zebrafish model of skin inflammation, we have found reduced levels of vitamin B6 and increased ones of cystathionine, a marker of vitamin B6 deficiency and of impaired biosynthesis of H2S. The main objective of this study was determining if vitamin B6 and H2S were able to inhibit skin inflammation.
Métodos:
Tnfr2-deficient zebrafish larvae of 24 hours post-fertilization (hpf)were treated by bath immersion with three vitamin B6 forms (vitamers), including pyridoxine, pyridoxal and pyridoxal-5’P (PLP), and the H2S donor GYY 4137 at 0-10 µM in the presence of 1% DMSO to facilitate adsorption. Skin inflammation was then evaluated at 72 hpf by checking neutrophil skin infiltration and H2O2 levels. Transcriptomic data from human psoriasis samples available at the GEO database were also analyzed.
Resultados:
We observed that pyridoxine was able to reduce neutrophil dispersion and H2O2 level of Tnfr2-deficient larvae in a dose-dependent manner. Similarly, pyridoxal and PLP had a similar effect to piridoxine. Strikingly, the genes encoding the two major enzymes involved in PLP biosynthesis (PDXK and PNPO) were upregulated and correlated with inflammation (IL1B expression) in psoriatic skin lesions, while those of the one responsible for its inactivation (PHOSPHO2) strongly decreased. In addition, CBS gene levels decreased in psoriatic lesional skin and negatively correlated with inflammation. These results suggest an altered biosynthesis of vitamin B6 and impaired production of H2S in psoriatic lesions.
Conclusiones:
The results of our study point out to vitamin B6 vitamers, cystathionine and H2S as prognosis markers for psoriasis and suggest that dietary intake of vitamin B6 may have a profound impact on this disease.
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