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Biomedical subjects

M Rendl

Publications and source records attributed to M Rendl.

7 recordsLinked to original sources
PubMed2001

Topically applied lactic acid increases spontaneous secretion of vascular endothelial growth factor by human reconstructed epidermis.

BACKGROUND: Alpha-hydroxy acids (AHAs) are widely used for the treatment of hyperkeratotic skin disorders and photodamaged skin. OBJECTIVES: To investigate the effect of lactic acid (LA) on the secretion of cytokines by keratinocytes (KCs) of human reconstructed epidermis. METHODS: Creams containing 1.5%, 3% or 5% LA or vehicle controls were topically applied on to human epidermal equivalents (EEs). After 24 h, EEs were analysed for morphology and for the presence of apoptotic cells. Secretion of vascular endothelial growth factor (VEGF), angiogenin (ANG) and interleukin (IL)-8 was measured in the supernatants by enzyme-linked immunosorbent assay. RESULTS: LA led to a concentration-dependent increase in apoptotic cells as determined by cell morphology and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling. VEGF secretion was increased 2.5- and 2.8-fold (P < 0.05) over vehicle control after treatment with 1.5% and 3% LA, respectively. No significant increase in VEGF secretion was detected with 5% LA. In contrast to VEGF, secretion of ANG was decreased by LA in a concentration-dependent manner (0.5-fold for 5% LA; P < 0.01). No significant changes in IL-8 secretion were found with any of the concentrations tested. CONCLUSIONS: Our data demonstrate that the topical application of AHAs modulates the secretion of cytokines by KCs. Regulation of KC-derived growth factors and cytokines by AHAs might represent a mechanism contributing to their therapeutic effects in disorders such as photoageing.

Administration, Topical↗
PubMed2000

Keratinocytes express the CD146 (Muc18/S-endo) antigen in tissue culture and during inflammatory skin diseases.

The CD146 (or MUC18/MEL-CAM) antigen is a cell adhesion molecule of the immunoglobulin superfamily. Besides in melanoma, expression of CD146 antigen has been demonstrated in breast epithelia and hair follicles. We studied its expression by human keratinocytes in culture as well as in neoplastic and inflammatory skin diseases. Staining of primary cultured keratinocytes revealed expression of CD146 on the cell membrane, preferentially on cell-cell contact sites. Western blot analysis of keratinocytes detected a band of approximately 113 kDa, corresponding to the CD146 protein. In contrast to primary keratinocytes, neither CD146 protein nor mRNA expression was found in the keratinocyte-derived cell lines A431 and HaCaT. Treatment of keratinocytes with the proinflammatory cytokines interleukin-1 and interleukin-6, tumor necrosis factor-alpha, and interferon-gamma, resulted in no change of CD146 expression and incubation with phorbol 12-myristate 13-acetate led to a reduction of CD146 on keratinocytes. By contrast, when culturing keratinocytes in medium devoid of growth supplements, a distinct upregulation was observed as compared with culture in fully supplemented medium. In normal human epidermis expression of the CD146 antigen was not detectable. It was strongly upregulated, however, on suprabasal keratinocytes in psoriasis, in lichen planus, in the epidermis overlying skin neoplasms, and in viral warts. In squamous cell carcinomas and basal cell carcinomas only a minority of tumor cells expressed CD146. Our findings suggest that the CD146 antigen represents an activation marker of keratinocytes and may be involved in cutaneous inflammatory tissue reaction.

Antigens, CD↗
PubMed2000

Terminal differentiation of human keratinocytes and stratum corneum formation is associated with caspase-14 activation.

Programmed cell death of epidermal keratinocytes (KC) results in the formation of cornified cells, which constitute the outermost skin layer, the stratum corneum. Here we show by reverse transcription-polymerase chain reaction, western blot, and immunohistochemistry that epidermal KC express caspase-14, a member of the caspase family of pro-apoptotic proteases, in a tissue-specific manner. Caspase-14 protein abundance strongly increases during terminal differentiation of KC in vivo and in vitro. Under conditions that lead to stratum corneum formation caspase-14 cleavage products, which indicate proenzyme activation, appeared in the KC lysates. Cleavage of the enzyme was also detected in lysates from normal human epidermis and in extracts of stratum corneum. Our findings demonstrate that caspase-14 is activated during KC differentiation and strongly suggest that it is involved in the formation of the human skin barrier.J Invest Dermatol 115:1148-1151 2000

Caspase 14↗
PubMed1998

Retinoids downregulate vascular endothelial growth factor/vascular permeability factor production by normal human keratinocytes.

Normal human keratinocytes (KC) are a prominent source of vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF), both in vivo and in tissue culture. In this report we have investigated the influence of retinoids, which are used to treat several skin diseases, on VEGF/VPF production by KC. All-trans retinoic acid (RA), 13-cis RA, and all-trans retinol reduced VEGF/VPF secretion by KC in primary cultures by a mean +/- SD of 58 +/- 25%, 46 +/- 21%, and 54 +/- 20%, respectively, compared with control values. Reductions were observed at concentrations as low as 10(-10)M for all-trans RA, a level that is easily reached in vivo during retinoid treatment. The reduction in VEGF/VPF protein by 10(-6)M all-trans RA was paralleled by a strong downregulation of VEGF/VPF mRNA levels. In contrast to normal KC, all-trans RA had no effect on the HaCaT keratinocyte cell line, and it stimulated VEGF/VPF release by the epidermoid carcinoma cell line A431 2-fold. Our data demonstrate that retinoids are potent inhibitors of VEGF/VPF production by normal human KC. Downregulation of VEGF/VPF production in these cells by retinoids may contribute to the therapeutic effects or retinoids in diseases that are accompanied by angioproliferation, such as psoriasis.

Cell Division↗
PubMed1998

Nitric oxide synthases in Kaposi's sarcoma are expressed predominantly by vessels and tissue macrophages.

Kaposi's sarcoma (KS) is a tumor of presumed vascular origin frequently found in patients with AIDS. Recent data suggest that the development of KS is linked with the presence of a newly recognized herpesvirus, human herpesvirus type 8. Nitric oxide (NO), a messenger molecule with vasoactive, antitumor, and antimicrobial effects, is produced by three isoforms of nitric oxide synthases (NOS). In the present report, we investigated the expression of NOS isoforms in KS. By NADPH-diaphorase histochemistry, NOS activity was detectable in endothelia and CD45+ cells within KS lesions. Reactivity for endothelial NOS (eNOS) was found in blood vessel endothelia; however, eNOS reactivity was negative in KS spindle cells in 12 of 17 tumors, and moderately positive in the other 5 lesions. In contrast to KS, tumor cells in three hemangiomas and one angiosarcoma were strongly positive for eNOS. Inducible NOS (iNOS) was absent from KS tumor cells but was found regularly in CD45+, HLA-DR+ cells within the lesions. In five KS-derived spindle cell cultures, neither eNOS nor iNOS proteins were detectable. The sporadic expression of eNOS by KS spindle cells in vivo and the absence of eNOS protein from KS spindle cells in tissue cultures argue against the possibility that the cells are derived from blood vessel endothelia. The consistent expression of iNOS by CD45+, HLA-DR+ cells within KS lesions strongly suggests that leukocyte-derived NO participates in the pathology of this tumor.

Endothelium, Vascular↗
PubMed1997

Differences in tumor microvessel density between squamous cell carcinomas and basal cell carcinomas may relate to their different biologic behavior.

Tumor microvessel density (TMVD) has been recognized as an important indicator for the metastatic risk in certain tumors. The purpose of this study was to analyse whether there is an association of TMVD in epithelial neoplasms of the skin with their clinical behavior. Paraffin sections of keratoacanthomas (KA, n = 10), squamous cell carcinomas (SCC, n = 9), nodular (nod-BCC, n = 13), and sclerosing (scl-BCC, n = 12) basal cell carcinomas were immunohistochemically stained for factor-VIII-related antigen and TMVD was determined. In all SCC, KA and nod-BCC, TMVD significantly exceeded perilesional skin microvessel density (PSMVD) (SCC:TMVD/PSMVD = 20.54:11.25, p < 0.0001; KA:TMVD/PSMVD = 20.90:12.17, p < 0.0001; nod-BCC:TMVD/PSMVD = 16.77:13.34, p = 0.03). In contrast, no significant difference between TMVD and PSMVD was found in scl-BCC (15.44:12.86, p = 0.22). TMVD was significantly higher in SCC and KA compared to nod-BCC (p = 0.036 and 0.006, respectively). Our data demonstrate that SCC and KA are highly vascularized tumors. The fact that TMVD does not differ significantly between SCC and KA (p = 0.80) suggests that MVD is not an indicator for the metastatic risk or aggressive growth behavior of epithelial skin tumors. The finding that MVD in both nod- and scl-BCC is significantly lower than in SCC and KA, might at least in part explain the slow growth of BCC.

Biopsy↗