| 1. |
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| 2. |
- Haak-Frendscho, M, et al.
(författare)
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Histidine decarboxylase expression in human melanoma.
- 2000
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Ingår i: Journal of Investigative Dermatology. - : Elsevier BV. - 0022-202X .- 1523-1747. ; 115:3, s. 345-52
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Tidskriftsartikel (refereegranskat)abstract
- Histamine has been implicated as one of the mediators involved in regulation of proliferation in both normal and neoplastic tissues. Histidine decarboxylase, the only enzyme that catalyzes the formation of histamine from L-histidine, is an essential regulator of histamine levels. In this study, we investigated the gene and protein expression of histidine decarboxylase in melanoma. Reverse transcriptase polymerase chain reaction and in situ hybridization studies of WM-35, WM-983/B, HT-168, and M1 human melanoma cell lines both resulted in positive signals for histidine decarboxylase messenger RNA. A polyclonal chicken antibody was developed against human histidine decarboxylase and protein expression was confirmed by western blot analysis of the cell lysates, revealing a predominant immunoreactive band at approximately 54 kDa corresponding to monomeric histidine decarboxylase. Protein expression of histidine decarboxylase was also shown by flow cytometric analysis and strong punctate cytoplasmic staining of melanoma cell lines. Moreover, both primary and metastatic human melanoma tissues were brightly stained for histidine decarboxylase. When compared with the very weak or no reactions on cultivated human melanocytes both western blot and immunohistochemical studies showed much stronger histidine decarboxylase expression in melanoma cells. These findings suggest that expression of histidine decarboxylase is elevated in human melanoma.
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| 3. |
- Nagy, István, et al.
(författare)
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Distinct strains of Propionibacterium acnes induce selective human beta-defensin-2 and interleukin-8 expression in human keratinocytes through toll-like receptors.
- 2005
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Ingår i: Journal of Investigative Dermatology. - 0022-202X .- 1523-1747. ; 124:5, s. 931-8
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Tidskriftsartikel (refereegranskat)abstract
- Acne is a chronic inflammatory disease of the pilosebaceous follicle. One of the main pathogenetic factors in acne is the increased proliferation of Propionibacterium acnes (P. acnes) in the pilosebaceous unit. We investigated whether direct interaction of P. acnes with keratinocytes might be involved in the inflammation and ductal hypercornification in acne. The capacities of different P. acnes strains to activate the innate immune response and the growth of cultured keratinocytes were investigated. We have found that two clinical isolates of P. acnes significantly induced human beta-defensin-2 (hBD2) messenger RNA (mRNA) expression; in contrast a third clinical isolate and the reference strain (ATCC11828) had no effect on hBD2 mRNA expression. In contrast, all four strains significantly induced the interleukin-8 (IL-8) mRNA expression. The P. acnes-induced increase in hBD2 and IL-8 gene expression could be inhibited by anti-Toll-like receptor 2 (TLR2) and anti-TLR4 neutralizing antibodies, suggesting that P. acnes-induced secretion of soluble factors in keratinocytes are both TLR2 and TLR4 dependent. In addition, the clinical isolate P. acnes (889) was capable of inducing keratinocyte cell growth in vitro. Our findings suggest that P. acnes modulates the antimicrobial peptide and chemokine expression of keratinocytes and thereby contributes to the recruitment of inflammatory cells to the sites of infections.
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| 4. |
- Széll, Márta, et al.
(författare)
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Proliferating keratinocytes are putative sources of the psoriasis susceptibility-related EDA+ (extra domain A of fibronectin) oncofetal fibronectin.
- 2004
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Ingår i: Journal of Investigative Dermatology. - 0022-202X .- 1523-1747. ; 123:3, s. 537-46
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Tidskriftsartikel (refereegranskat)abstract
- The extra domain A of fibronectin (EDA+ oncofetal isoform of fibronectin was recently reported to be overexpressed in psoriatic uninvolved epidermis. It has been proposed that the abnormal presence of EDA+ oncofetal protein at the dermal-epidermal junction in the uninvolved skin may provide the "psoriatic" environment in which keratinocytes are in a preactivated state with regard to mitogenic signals (e.g., T cell lymphokines). To determine the possible sources of cellular fibronectin in the non-lesional psoriatic skin, we aimed to investigate whether keratinocytes could produce the EDA+ oncofetal form of fibronectin. RT-PCR studies revealed that both cultured normal keratinocytes and HaCaT cells express the EDA+ splice variant of fibronectin mRNA, and in HaCaT cells the EDA+/EDA- transcript ratio was elevated compared with normal keratinocytes. Cultured keratinocytes and HaCaT cells showed intracytoplasmic staining with an EDA+ fibronectin-specific antibody and among the positively stained cells many showed mitosis. Using RT-PCR, western blot analysis, and flow cytometry, we showed that in synchronized HaCaT cells the amount of both total fibronectin and its EDA+ isoform change with the proliferation/differentiation state of HaCaT cells and peak in highly proliferating cells. We show that in short-term ex vivo cultures, a small population of EDA+ fibronectin containing cell population appear among psoriatic uninvolved, but not normal epidermal cells. We also demonstrate that cell attachment has a strong influence on the expression of both total and EDA+ fibronectin. Our results suggest that proliferating keratinocytes could be the sources of the psoriasis susceptibility-related EDA+ oncofetal fibronectin in the epidermis.
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| 5. |
- Szolnoky, G, et al.
(författare)
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A mannose-binding receptor is expressed on human keratinocytes and mediates killing of Candida albicans.
- 2001
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Ingår i: Journal of Investigative Dermatology. - : Elsevier BV. - 0022-202X .- 1523-1747. ; 117:2, s. 205-13
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Tidskriftsartikel (refereegranskat)abstract
- Human keratinocytes are known to kill Candida albicans in vitro, but the mechanism of killing is not yet understood. Here, we demonstrate that spontaneous, ultraviolet-B-light-induced, alpha-melanocyte-stimulating-hormone-induced, and interleukin-8-induced Candida killing by keratinocytes can be inhibited with mannan and mannosylated bovine serum albumin (Man-BSA). A polyclonal goat serum raised against the human macrophage mannose receptor stained suprabasal keratinocytes, but no staining was observed on keratinocytes with a monoclonal antibody (mAb15) specific for the human macrophage mannose receptor. Mannose-affinity chromatography of keratinocyte extract isolated a 200 kDa protein, and on the Western blot the goat antiserum reacted with a 200 kDa protein. In radioligand binding studies, the binding of 125I-Man-BSA to human keratinocytes was inhibited by mannan in a concentration-dependent manner. Analysis of the binding revealed a single class keratinocyte mannose receptor with a KD of 1.4 x 10(-8) M and a Bmax of 1 x 10(4) binding sites per cell. The binding of 125I-Man- BSA to keratinocytes proved to be time-dependent, acid-precipitable, and Ca2+- and trypsin-sensitive. After trypsinization the receptors underwent a rapid recovery at 37 degrees C. These results demonstrate the presence of mannose receptor on human keratinocytes, and its active involvement in the killing of Candida albicans.
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| 6. |
- Mørk, Cato, et al.
(författare)
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Microvascular arteriovenous shunting is a probable pathogenetic mechanism in erythromelalgia
- 2000
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Ingår i: Journal of Investigative Dermatology. - : Elsevier BV. - 0022-202X .- 1523-1747. ; 114:4, s. 643-646
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Tidskriftsartikel (refereegranskat)abstract
- Erythromelalgia is a condition consisting of red, warm, and burning painful extremities. Symptoms are relieved by cold and aggravated by heat. A wide variety of etiologic conditions can cause erythromelalgia, but one common pathogenetic mechanism, microvascular arteriovenous shunting, has been hypothesized. The aim of this study was to test this hypothesis. Quantification of skin microvascular perfusion using laser Doppler perfusion imaging and skin temperature at rest and after central body heating was performed in 14 patients with erythromelalgia and 11 controls. Attacks of erythromelalgia were induced in eight patients after heat provocation. In the plantar region of the foot, the location of numerous anatomical arteriovenous shunts, these patients significantly increased the skin perfusion as compared with asymptomatic patients with erythromelalgia and controls. In the dorsal region with few arteriovenous shunts no significant differences between the groups were demonstrated. The results show a relation between clinical symptoms and increased perfusion in the region of numerous anatomical arteriovenous shunts, and support the hypothesis of increased thermoregulatory arteriovenous shunt flow during attacks in primary erythromelalgia.
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| 7. |
- Allhorn, Maria, et al.
(författare)
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Heme-Scavenging Role of alpha1-Microglobulin in Chronic Ulcers.
- 2003
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Ingår i: Journal of Investigative Dermatology. - : Elsevier BV. - 1523-1747 .- 0022-202X. ; 121:3, s. 640-646
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Tidskriftsartikel (refereegranskat)abstract
- Chronic venous ulcers are characterized by chronic inflammation. Heme and iron, originating from blood cell hemolysis as well as extravascular necrosis, have been implicated as important pathogenic factors due to their promotion of oxidative stress. It was recently reported that the plasma and tissue protein alpha1-microglobulin is involved in heme metabolism. The protein binds heme, and a carboxy-terminally processed form, truncated alpha1-microglobulin, also degrades heme. Here, we show the presence of micromolar levels of heme and free iron in chronic leg ulcer fluids. Micromolar amounts of alpha1-microglobulin was also present in the ulcer fluids and bound to added radiolabeled heme. Truncated alpha1-microglobulin was found in the ulcer fluids and exogenously added alpha1-microglobulin was processed into the truncated alpha1-microglobulin form. Histochemical analysis of chronic wound tissue showed the presence of iron deposits, heme/porphyrins in infiltrating cells basement membranes and fibrin cuffs around vessels, and alpha1-microglobulin ubiquitously distributed but especially abundant in basement membranes around vessels and at fibrin cuffs. Our results suggest that alpha1-microglobulin constitutes a previously unknown defense mechanism against high heme and iron levels during skin wound healing. Excessive heme and iron, which are not buffered by alpha1-microglobulin, may underlie the chronic inflammation in chronic ulcers.
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| 8. |
- Mirastschijski, Ursula, et al.
(författare)
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Matrix metalloproteinase inhibitor BB-3103 unlike the serine proteinase inhibitor aprotinin abrogates epidermal healing of human skin wounds ex vivo.
- 2002
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Ingår i: Journal of Investigative Dermatology. - : Elsevier BV. - 1523-1747 .- 0022-202X. ; 118:1, s. 55-64
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Tidskriftsartikel (refereegranskat)abstract
- Several matrix metalloproteinases and serine proteinases are upregulated in migrating keratinocytes during cutaneous wound repair. Single cell culture studies indicate the necessity for matrix metalloproteinases but not for serine proteinases in keratinocyte locomotion. To account for epithelial-mesenchymal interactions, an ex vivo human skin wound model was used to investigate the contribution of matrix metalloproteinases and serine proteinases to wound healing by treatment with broad-spectrum inhibitors of matrix metalloproteinases (BB-3103) or serine proteinases (aprotinin). Human skin explants with circular 3 mm superficial defects were incubated in culture medium without (controls) or with the proteinase inhibitors for 7 d. BB-3103 abrogated epithelialization (p < 0.001), whereas aprotinin-treated wounds and controls were covered with new epithelium. Lack of epithelialization was unlikely due to cytotoxicity because the matrix metalloproteinase inhibitor did neither influence viability of cultured epidermal keratinocytes nor apoptosis in wounds. Involvement of specific matrix metalloproteinases in epithelialization was analyzed by gelatin zymography, western blotting, immunohistochemistry, and in situ hybridization. Wound healing was accompanied by active matrix metalloproteinase-1 and increased active matrix metalloproteinase-2 but irrespectively of active matrix metalloproteinase-9. BB-3103 blocked activation of matrix metalloproteinase-2 and matrix metalloproteinase-9 but not of matrix metalloproteinase-1. Active matrix metalloproteinase-2 localized solely to the dermis, whereas matrix metalloproteinase-9 was consistently found in new epithelium. Membrane-type 1 matrix metalloproteinase was undetectable in wound keratinocytes. BB-3103 and aprotinin reduced tumor necrosis factor-alpha in media but did not appreciably alter amounts of other soluble regulators of matrix metalloproteinases and epithelialization. Our findings demonstrate that keratinocyte migration is associated with active matrix metalloproteinase-2 but occurs independently of serine proteinases and active matrix metalloproteinase-9 in fibrin-deficient skin wound healing.
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| 9. |
- Mørk, Cato, et al.
(författare)
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The Prostaglandin E1 Analog Misoprostol Reduces Symptoms and Microvascular Arteriovenous Shunting in Erythromelalgia : A Double-Blind, Crossover, Placebo-Compared Study
- 2004
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Ingår i: Journal of Investigative Dermatology. - : Nature Publishing Group. - 0022-202X .- 1523-1747. ; 122:3, s. 587-593
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Tidskriftsartikel (refereegranskat)abstract
- Based on previous experience with parenteral prostanoids, we studied the effect of misoprostol treatment, an orally administered prostaglandin E1 analog, in patients with erythromelalgia. Treatment with placebo was followed by treatment with misoprostol (0.4–0.8 mg per d), both for 6 wk. The patients (n=21) and a study nurse who administered the trial were blinded. The endpoints were change in pain and need for cooling and global assessment of the treatment. Following central body heat provocation, global skin perfusion, capillary morphology, and change in pain were also recorded before and after each treatment period. Results were compared with data from healthy control subjects (n=11) that did not undergo treatment. Clinical safety and tolerability evaluation included physical examinations, clinical laboratory tests, and monitoring of adverse events. All clinical outcome measures were significantly better after treatment with misoprostol (p<0.01) as compared with placebo treatment and after a 3-mo follow-up without treatment. The heat-induced increase in global perfusion after misoprostol treatment was similar to the control group and significantly lower when compared with baseline (p<0.01) and placebo treatment (p<0.05), respectively. This study demonstrates that misoprostol is clinically superior to placebo in patients with erythromelalgia. The results of the perfusion studies may imply that the mechanism of action of the beneficial effect of misoprostol is reduced microvascular arteriovenous shunting in affected skin.
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| 10. |
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