Upregulation of 8-lipoxygenase in the dermatitis of IkappaB-alpha-deficient mice.

Schneider C, Strayhorn WD, Brantley DM, Nanney LB, Yull FE, Brash AR
J Invest Dermatol. 2004 122 (3): 691-8

PMID: 15086555 · DOI:10.1111/j.0022-202X.2004.22329.x

Neonatal mice deficient in IkappaB-alpha, an inhibitor of the ubiquitous transcription factor NF-kappaB, develop severe and widespread dermatitis shortly after birth. In humans, inflammatory skin disorders such as psoriasis are associated with accumulation in the skin of the unusual arachidonic acid metabolite 12R-hydroxyeicosatetraenoic acid (12R-HETE), a product of the enzyme 12R-lipoxygenase. To examine the etiology of the murine IkappaB-alpha-deficient skin phenotype, we investigated the expression of lipoxygenases and the metabolism of exogenous arachidonic acid in the skin. In the IkappaB-alpha-deficient animals, the major lipoxygenase metabolite was 8S-HETE, formed together with a minor amount of 12S-HETE; 12R-HETE synthesis was undetectable. Skin from the wild-type littermates formed 12S-HETE as the almost exclusive lipoxygenase metabolite. Upregulation of 8S-lipoxygenase (8-LOX) in IkappaB-alpha-deficient mice was confirmed at the transcriptional and translational level using ribonuclease protection assay and western analysis. In immunohistochemical studies, increased expression of 8-LOX was detected in the stratum granulosum of the epidermis. In the stratum granulosum, 8-LOX may be involved in the terminal differentiation of keratinocytes. Although mouse 8S-lipoxygenase and human 12R-lipoxygenase are not ortholog genes, we speculate that in mouse and humans the two different enzymes may fulfill equivalent functions in the progression of inflammatory dermatoses.

MeSH Terms (13)

Animals Arachidonate 12-Lipoxygenase Arachidonate Lipoxygenases Arachidonic Acid Blotting, Western Dermatitis Humans I-kappa B Proteins Immunohistochemistry Mice NF-KappaB Inhibitor alpha Skin Up-Regulation

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