DIANA GARCIA MORENO, FRANCISCO JAVIER MARTÍNEZ MORCILLO, FRANCISCO JUAN MARTINEZ NAVARRO, MARÍA TERESA MARTÍNEZ MENCHÓN, ANTONIO RAUL CORBALÁN VÉLEZ, JOSE MESEGUER PEÑALVER, VICTORIANO MULERO MÉNDEZ,

• [GI/IMIB/C060/2011] Inmunidad, inflamación y cáncer
• [GI/IMIB/C003/2011] Cirugía digestiva, endocrina y trasplante de órganos abdominales
• [GI/IMIB/C006/2011] INMUNOLOGÍA E INMUNOTOLERANCIA EN TRASPLANTES Y ENFERMEDADES DE BASE INMUNOLÓGICA

Psoriasis is a chronic inflammatory dermatosis that affects millions of people worldwide. Tumor necrosis factor ? (TNF?) is a multifunctional cytokine that mediates key roles in acute and chronic inflammation, including psoriasis. In previous studies, we have taken advantage of the strengths of the zebrafish embryo for in vivo imaging to develop a skin inflammation model based in the genetic depletion of Tnfa or its receptor Tnfr2 where inflammation can be easily quantified by assessing neutrophil mobilization to the skin

The expression of genes encoding key enzymes in NAD+ biosynthesis were obtained from transcriptomic data of human psoriasis samples available at the GEO database. RT-qPCR was used to determine the expression of these genes in zebrafish larvae deficient in Tnfr2. The ability of NAD+ and its precursors applied by bath immersion to reduce neutrophil dispersion was evaluated in Tnfr2-deficient larvae, as an indicator of skin inflammation severity

Our results show that the genes encoding the enzymes involved in the biosynthesis of NAD+ are altered in both human psoriatic lesional skin and Tnfr2-deficient zebrafish. In addition, NAD+ was able to reduce neutrophil dispersion of Tnfr2-deficient larvae while, conversely, its precursors nicotinamide, nicotinamide monunucleotide and nicotinic acid promoted neutrophil dispersion in wild type larvae.

These results suggest that pharmacological manipulation of NAD+ biosynthesis could reduce skin inflammation and psoriasis progression. Studies are in progress to validate nicotinic acid, nicotinamide, nicotinamide monunucleotide and NAD+ serum levels as prognosis markers of psoriasis and to elucidate the molecular mechanisms involved in the regulation of skin inflammation by these metabolites.