Identification of differentially expressed genes in cutaneous squamous cell carcinoma by microarray expression profiling.

Background: Carcinogenesis is a multi-step process indicated by several genes up- or down-regulated during tumor progression. This study examined and identified differentially expressed genes in cutaneous squamous cell carcinoma (SCC).

Results: Three different biopsies of 5 immunosuppressed organ-transplanted recipients each normal skin (all were pooled), actinic keratosis (AK) (two were pooled), and invasive SCC and additionally 5 normal skin tissues from immunocompetent patients were analyzed.

Expression regulation of MAO isoforms in monocytic cells in response to Th2 cytokines.

Background: Th2-cytokines, such as interleukins-4 and -13 (IL-4, IL-13), have been identified as alternative stimuli of monocytes/macrophages. We have recently profiled the gene-expression pattern of IL-4-treated human peripheral monocytes and found that 15-lipoxygenase-1 (15-LOX1) and monoamine oxidase A (MAO-A) are among the five most strongly upregulated gene products in IL-4-treated cells. Transfection of monocytic cells (U937) with 15-LOX1 also induced MAO-A expression.

Gene expression alterations of human peripheral blood monocytes induced by medium-term treatment with the TH2-cytokines interleukin-4 and -13.

The TH2-cytokines interleukins-4 and -13 severely alter gene expression of monocytic cells. We quantified the impact of interleukins-4 and -13 on the gene expression pattern of human peripheral blood monocytes applying a strategy that involved microarray hybridization, RT-PCR, immunohistochemistry and activity assays. After 3 days of continuous cytokine exposure the six most strongly upregulated gene products (15-lipoxygenase-1, fibronectin, monoamine oxidase-A, CD1c, CD23A, coagulation factor XIII) included four proteins with potential anti-inflammatory properties: (i) 15-lipoxygenase-1 (290-fold upregulation), (ii) fibronectin (180-fold upregulation), (iii) monoamine oxidase-A (56-fold upregulation) and (iv) coagulation factor XIII (35-fold upregulation).

Expression of 12/15-lipoxygenase attenuates intracellular lipid deposition during in vitro foam cell formation.

Objective: Lipoxygenases with different positional specificity have been implicated in atherogenesis, but the precise roles of the various isoforms remain unclear. Because of its capability of oxidizing low-density lipoprotein (LDL) to an atherogenic form, 12/15-lipoxygenases have been suggested to initiate LDL oxidation in vivo; thus, these enzymes may exhibit pro-atherogenic activities. However, in several rabbit atherosclerosis models, the enzyme appears to act atheroprotective.

Th2 response of human peripheral monocytes involves isoform-specific induction of monoamine oxidase-A.

Monocyte/macrophage function is critically regulated by specific cytokines and growth factors that they are exposed to at inflammatory sites. IL-4 and IL-13 are multifunctional cytokines generated mainly by Th2 lymphocytes that have important biological activities in allergy and inflammation. The Th2 response of human peripheral monocytes is characterized by complex alterations in the gene expression pattern, which involves dominant expression of CD23 cell surface Ag and lipid-peroxidizing 15-lipoxygenase-1 (15-LOX1).

Mammalian arachidonate 15-lipoxygenases structure, function, and biological implications.

Lipoxygenases (LOXs) constitute a heterogeneous family of lipid peroxidizing enzymes capable of oxygenating polyunsaturated fatty acids to their corresponding hydroperoxy derivatives. In mammals, LOXs are classified with respect to their positional specificity of arachidonic acid oxygenation into 5-, 8-, 12-, and 15-LOXs. Arachidonate 15-LOXs may be sub-classified into a reticulocyte-type (type-1) and an epidermis-type (type-2) enzyme.