Gerhard Fürstenberger — Page 2

PubMed2002

Arachidonate 8(S)-lipoxygenase.

The recently identified mouse 8(S)-lipoxygenase almost exclusively directs oxygen insertion into the 8(S) position of arachidonic acid and, with lower efficiency, into the 9(S) position of linoleic acid. The protein of 677 amino acids displays 78% sequence identity to human 15(S)-lipoxygenase-2 which is considered to be its human orthologue. The 8(S)-lipoxygenase gene, Alox15b, consisting of 14 exons and spanning 14.5 kb is located within a gene cluster of related epidermis-type lipoxygenases at the central region of mouse chromosome 11. 8(S)-Lipoxygenase is predominantly expressed in stratifying epithelia of mice, constitutively in the hair follicle, forestomach, and foot-sole and inducible in the back skin with strain-dependent variations. The expression is restricted to terminally differentiating keratinocytes, in particular the stratum granulosum and 8(S)-lipoxygenase activity seems to be involved in terminal differentiation of mouse epidermis. Tumor-specific up-regulation of 8(S)-lipoxygenase expression and activity indicate a critical role of this enzyme in malignant progression during tumor development in mouse skin.

Animals↗

PubMed2002

The effects of cyclooxygenase isozyme inhibition on incisional wound healing in mouse skin.

In addition to their proinflammatory activities, prostaglandins recently have been shown to be beneficial in the resolution of tissue injury and inflammation. Thus, inhibition of cyclooxygenase-2, the predominant prostaglandin endoperoxide synthase under these conditions, may not only result in attenuating the inflammatory response but also in delaying tissue regeneration and repair. To this end, we investigated cyclooxygenase isozyme expression and the effects of cyclooxygenase inhibitors on wound healing upon full-thickness incisions in mouse skin. Immunohistochemical analysis revealed prominent expression of cyclooxygenase isozymes in keratinocytes of the hyperplastic epithelium, with cyclooxygenase-1 immunosignals predominating in the suprabasal compartment and cyclooxygenase-2 immunosignals spread throughout the whole epidermis. Moreover, dendritic cells, resembling Langerhans cells, as well as endothelial cells and macrophages in the vicinity of or within the granulation tissue were found to express both isozymes. Inhibition of prostaglandin E2 synthesis by oral administration of the cyclooxygenase-1-selective inhibitor SC-560 or the cyclooxygenase-2-selective inhibitor valdecoxib did not retard wound healing in mouse skin macroscopically. Except for a slight transient retardation of epithelialization early after wounding wound-induced neoangiogenesis, collagen deposition, and the restoration of tensile strength were not delayed by these agents. Likewise, the nonselective inhibitor indomethacin had no effect on the tensile strength of incisional skin wounds.

Acute Disease↗