Eicosanoids in Psoriasis – 15-HETE on the Stage

Kragballe, Knud; Voorhees, John J.

doi:10.1159/000249181

Cited by 21 publications

(4 citation statements)

References 20 publications

(21 reference statements)

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“…A further novel, and intriguing, finding was the significant UVB up-regulation of the anti-inflammatory eicosanoid 15-HETE, exhibiting a later response with mean levels observed to double between 48 and 72 h and potentially rising beyond 72 h. This 15-LOX metabolite has been shown to inhibit the synthesis of proinflammatory eicosanoids PGE 2 and 12-HETE in in vitro models (14 , 44) and to inhibit the activity of 12-LOX in epidermis (45) and 5-LOX in neutrophils (44) . Hence, the later elevation of this mediator could reflect a role in the resolution of sunburn, including limitation of the neutrophil influx.…”

Section: Discussionmentioning

confidence: 99%

The sunburn response in human skin is characterized by sequential eicosanoid profiles that may mediate its early and late phases

et al. 2009

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Sunburn is a commonly occurring acute inflammatory process, with dermal vasodilatation and leukocyte infiltration as central features. Ultraviolet (UV) B-induced hydrolysis of membrane phospholipids releases polyunsaturated fatty acids, and their subsequent metabolism by cyclooxygenases (COXs) and lipoxygenases (LOXs) may produce potent eicosanoid mediators modulating different stages of the inflammation. Our objective was to identify candidate eicosanoids formed during the sunburn reaction in relation to its clinical and histological course. We exposed skin of healthy humans (n=32) to UVB and, for 72 h, examined expression of proinflammatory and anti-inflammatory eicosanoids using LC/ESI-MS/MS, and examined immunohistochemical expression of COX-2, 12-LOX, 15-LOX, and leukocyte markers, while quantifying clinical erythema. We show that vasodilatory prostaglandins (PGs) PGE2, PGF2α, and PGE3 accompany the erythema in the first 24–48 h, associated with increased COX-2 expression at 24 h. Novel, potent leukocyte chemoattractants 11-, 12-, and 8-monohydroxy-eicosatetraenoic acid (HETE) are elevated from 4 to 72 h, in association with peak dermal neutrophil influx at 24 h, and increased dermal CD3+ lymphocytes and 12- and 15-LOX expression from 24 to 72 h. Anti-inflammatory metabolite 15-HETE shows later expression, peaking at 72 h. Sunburn is characterized by overlapping sequential profiles of increases in COX products followed by LOX products that may regulate subsequent events and ultimately its resolution.—Rhodes, L. E., Gledhill, K., Masoodi, M., Haylett, A. K., Brownrigg, M., Thody, A. J., Tobin, D. J., Nicolaou, A. The sunburn response in human skin is characterized by sequential eicosanoid profiles that may mediate its early and late phases.

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Section: Discussionmentioning

confidence: 99%

The sunburn response in human skin is characterized by sequential eicosanoid profiles that may mediate its early and late phases

et al. 2009

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“…Intracellular FA transport in human epidermis is performed by specific carriers, such as the epidermal-type fatty acid-binding protein (E-FABP) [5][6][7] and the recently described FA-p34 complex composed of the Ca# + -binding proteins (CaBPs) S100A8 and S100A9 [8]. The fact that E-FABP and FA-p34 are highly overexpressed in lesional psoriatic skin [8][9][10] is in line with the discovery of an altered epidermal Ca# + gradient [11] and an altered FA transport\metabolism associated with this disease [12][13][14]. S100A7, a CaBP of unknown biological function, is weakly expressed in the granular layer of normal skin, whereas it is highly expressed in the cytosol and the particulate fraction of psoriatic epidermis [15][16][17].…”

Section: Introductionmentioning

confidence: 89%

Calcium-binding protein S100A7 and epidermal-type fatty acid-binding protein are associated in the cytosol of human keratinocytes

Hagens

Masouyé

Augsburger

et al. 1999

Biochemical Journal

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Expression of epidermal-type fatty acid-binding protein (E-FABP) and S100A7 has previously been shown to be elevated in psoriatic skin, a disease characterized by abnormal keratinocyte differentiation. However, no causal relationship between the up-regulation of these proteins and the disease has been shown. E-FABP is thought to be involved in cytosolic fatty acid (FA) transport, whereas the role of S100A7 is still unknown. In this report, we show by overlay assays that E-FABP, immobilized on nitrocellulose, is able to capture S100A7 from cytosolic psoriatic protein extracts and vice versa, suggesting the formation of a complex between the two proteins. Using purified E-FABP and S100A7, the complex can be reconstituted only in presence of EDTA. Moreover, we show that increased EDTA concentrations in psoriatic cytosolic protein extracts enhance complex formation. Partial complex disruption was obtained by the addition of physiological concentrations of Zn2+ (0.1 mM), whereas Ca2+ at 5 mM and Mg2+ at 30 mM had no effect. On the other hand, high Ca2+ concentrations (30 mM) resulted in partial complex disruption. Oleic acid-binding properties were observed for free E-FABP and the complex E-FABP-S100A7, but not for free S100A7. By using confocal microscopy we show that S100A7 and E-FABP are co-localized in the cytoplasm of differentiating keratinocytes from lesional psoriatic skin. These data indicate that formation of the E-FABP-S100A7 complex and its FA-binding function might be regulated at least by bivalent cations.

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“…Thus, S100A7 and EFABP could function to transport and/or metabolize fatty acids, including oleic acid (Hagens et al, 1999b). Other S100 proteins have also been implicated in fatty acid processing, including S100A8 and S100A9 (Kragballe and Voorhees, 1987;Fogh et al, 1989;Siegenthaler et al, 1997).…”

Section: S100a7 Colocalizes With A-actininmentioning

confidence: 99%

S100A7 (Psoriasin) Interacts with Epidermal Fatty Acid Binding Protein and Localizes in Focal Adhesion-Like Structures in Cultured Keratinocytes

Ruse

Broome

Eckert

2003

Journal of Investigative Dermatology

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S100 proteins are calcium-responsive signaling proteins that are overexpressed in cancer and inflammatory diseases. They act by forming complexes with target proteins to modify target protein function. Identifying S100 intracellular distribution, site of action, and protein targets are important goals. S100A7 (psoriasin) is an important member of this family that is markedly overexpressed in psoriatic keratinocytes; however, its role in disease progression is poorly understood. In this study, we express S100A7 in normal keratinocytes as a means to study S100A7 function. We show that S100A7 is present in the cytosol and in BiP/GRP78-positive (endoplasmic reticulum) tubular structures. When cells are challenged with elevated intracellular calcium, cytoplasmic S100A7 redistributes to alpha-actinin- and paxillin-positive peripheral structures that contact the substrate surface. Epidermal fatty acid binding protein is also overexpressed in psoriasis, and is a putative target of S100A7 in keratinocytes. To study this interaction, we coexpressed S100A7 and epidermal fatty acid binding protein. These studies indicate that S100A7 and epidermal fatty acid binding protein colocalize in the cytoplasm in untreated cultures, and localize in peripheral structures in response to calcium challenge. In addition, S100A7 expression appears to stabilize epidermal fatty acid binding protein level, and vice versa. Moreover, the proteins can be coprecipitated in the presence of bifunctional cross-linker, suggesting that they are part of a common complex. The colocalization with alpha-actinin and paxillin suggests that S100A7 and epidermal fatty acid binding protein colocalize in focal adhesion-like structures following calcium treatment.

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Eicosanoids in Psoriasis – 15-HETE on the Stage

Cited by 21 publications

References 20 publications

The sunburn response in human skin is characterized by sequential eicosanoid profiles that may mediate its early and late phases

The sunburn response in human skin is characterized by sequential eicosanoid profiles that may mediate its early and late phases

Calcium-binding protein S100A7 and epidermal-type fatty acid-binding protein are associated in the cytosol of human keratinocytes

S100A7 (Psoriasin) Interacts with Epidermal Fatty Acid Binding Protein and Localizes in Focal Adhesion-Like Structures in Cultured Keratinocytes

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