PubMed Health⌕ Search

Biomedical subjects

N Johansson

Publications and source records attributed to N Johansson.

At least 19 recordsLinked to original sources
PubMed2001

Levels of ochratoxin A in blood from Norwegian and Swedish blood donors and their possible correlation with food consumption.

Blood levels of ochratoxin A were determined in 406 Scandinavian blood donors (206 from Oslo, Norway, and 200 from Visby on the island of Gotland, Sweden), using an HPLC method. In connection with the blood collection, the subjects were asked to fill in a food questionnaire to obtain individual dietary information relevant to ochratoxin A exposure. The mean plasma level of ochratoxin A was 0.18 ng/ml in Oslo and slightly higher, 0.21 ng/ml (P=0.046) in Visby. There was no correlation between plasma levels of ochratoxin A and the estimated total dietary intake of ochratoxin A based on consumption data and levels in food (retrieved from the literature), neither was the plasma level of ochratoxin A correlated with the total amount of food consumed. However, consumption of several foods, including cereal products, wine, beer and pork, were to some minor degree related to high plasma levels of ochratoxin A. The strongest correlations (correlation coefficient r>0.4; P<0.001) were observed for women in relation to the consumption of beer or medium brown bread. Correlation analysis of combinations of two or more food categories did not result in any statistically significant correlation.

Adult↗
PubMed2001

Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human chondrosarcomas.

The aim of the present study was to characterise the ability of malignant chondrosarcomas to invade normal bone by analysing their production of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). For this purpose 12 chondrosarcomas were investigated for the expression of mRNAs for several MMPs and all 4 TIMPs by Northern hybridisation, and for immunohistochemical localisation of the proteins. A characteristic finding of these analyses was increased expression of MMP-13, MMP-14 and TIMP-2 mRNAs in chondrosarcomas when compared with nonmalignant control samples. Individual chondrosarcomas also exhibited elevated levels of MMP-1, MMP-7 and MMP-9 mRNAs. The results of Northern hybridisations were supported by immunohistochemical stainings of the corresponding tumour areas for MMP-2, MMP-14 and TIMP-2, further suggesting that these may have prognostic value for determining whether individual chondrosarcomas are locally aggressive or have a probability of recurrence. Another finding of the present study was a marked heterogeneity in histologic appearance and gene expression of the chondrosarcomas, emphasising the importance of analysing several areas of these tumours to get representative results. These findings suggest that analysis of MMPs could be a useful diagnostic indicator in patients with cartilaginous tumours and could help in differentiating between a low-grade malignant chondrosarcoma and a benign growing enchondroma.

Adolescent↗
PubMed2000

Matrix metalloproteinases in tumor invasion.

Controlled degradation of extracellular matrix (ECM) is essential for the growth, invasion, and metastasis of malignant tumors, and for tumor-induced angiogenesis. Matrix metalloproteinases (MMPs) are a family of zinc-dependent neutral endopeptidases collectively capable of degrading essentially all ECM components and they apparently play an important role in all these aspects of tumor development. Furthermore, recent evidence suggests that MMPs also play a role in tumor cell survival. In this review, we discuss the current concept concerning the role of MMPs and their inhibitors in tumor invasion, as a basis for prognosis and targeted therapeutic intervention in cancer.

Animals↗
PubMed2000

Inhibition of collagenase-3 (MMP-13) expression in transformed human keratinocytes by interferon-gamma is associated with activation of extracellular signal-regulated kinase-1,2 and STAT1.

Collagenase-3 (MMP-13) is characterized by an exceptionally wide substrate specificity and restricted expression. MMP-13 is specifically expressed by transformed human keratinocytes in squamous cell carcinomas in vivo and its expression correlates with their invasion capacity. Here, we show, that interferon-gamma (IFN-gamma) markedly inhibits expression of MMP-13 by human cutaneous SCC cells (UT-SCC-7) and by ras-transformed human epidermal keratinocytes (A-5 cells) at the transcriptional level. In addition, IFN-gamma inhibits collagenase-1 (MMP-1) expression in these cells. IFN-gamma abolished the enhancement of MMP-13 and MMP-1 expression by transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha), and inhibited invasion of A-5 cells through type I collagen. IFN-gamma also rapidly and transiently activates extracellular signal-regulated kinase 1,2 (ERK1,2) and blocking ERK1,2 pathway (Raf/MEK1,2/ERK1,2) by specific MEK1,2 inhibitor PD98059 partially (by 50%) prevents Ser-727 phosphorylation of STAT1 and suppression of MMP-13 expression by IFN-gamma. Furthermore, Ser-727 phosphorylation of STAT1 by ERK1,2, or independently of ERK1,2 activation is associated with marked reduction in MMP-13 expression. These observations identify a novel role for IFN-gamma as a potent inhibitor of collagenolytic activity and invasion of transformed squamous epithelial cells, and show that inhibition of MMP-13 expression by IFN-gamma involves activation of ERK1,2 and STAT1.

Cell Line, Transformed↗
PubMed2000

Expression of collagenase-3 (MMP-13) and collagenase-1 (MMP-1) by transformed keratinocytes is dependent on the activity of p38 mitogen-activated protein kinase.

Collagenase-3 (MMP-13) is a human matrix metalloproteinase specifically expressed by transformed squamous epithelial cells, i.e. squamous cell carcinoma (SCC) cells in culture and in vivo. Here, we have elucidated the signaling pathways regulating MMP-13 expression in transformed human epidermal keratinocytes, i.e. ras-transformed HaCaT cell line A-5 and cutaneous SCC cell line (UT-SCC-7). Treatment with tumor necrosis factor-(alpha) (TNF-(alpha) resulted in activation of extracellular signal-regulated kinase (ERK)1,2, Jun N-terminal kinase and p38 mitogen-activated protein kinase (MAPK) in both cell lines. In addition, transforming growth factor-(beta) (TGF-(beta) activated p38 MAPK in both cell lines, and ERK2 in A-5 cells. Selective inhibition of p38 activity with SB 203580 abolished the enhancement of MMP-13, as well as collagenase-1 (MMP-1) and 92-kDa gelatinase (MMP-9) expression by TNF-(alpha) and TGF-(beta). Blocking the ERK1, 2 pathway by PD 98059 had no effect on the induction of MMP-13 expression by TNF-(alpha) or TGF-(beta), but potently suppressed MMP-1 and MMP-9 production. Inhibition of p38 activity by SB 203580 also suppressed collagenolytic activity produced by both cell lines and inhibited invasion of TNF-(alpha) or TGF-(beta) stimulated A-5 cells through type I collagen and reconstituted basement membrane (Matrigel). These results show that activation of p38 MAPK pathway plays a crucial role in the invasive phenotype of transformed squamous epithelial cells, suggesting p38 MAPK as a target to specifically inhibit their invasion.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed2000

Matrix metalloproteinases in squamous cell carcinoma.

Controlled degradation of extracellular matrix (ECM) is essential in many physiological situations including developmental tissue remodeling, angiogenesis, tissue repair, and normal turnover of ECM. In addition, degradation of matrix components is an important feature of tumor growth, invasion, metastasis, and tumor-induced angiogenesis. Matrix metallo-proteinases (MMPs) are a family of zinc-dependent neutral endopeptidases, which are collectively capable of degrading essentially all ECM components. MMPs apparently play an important role in all the above mentioned aspects of tumor development. In addition, there is recent evidence that MMP activity is required for tumor cell survival. At present, several MMP inhibitors are in clinical trials of malignant tumors of different histogenetic origin. In this review we discuss the current view on the role of MMPs and their inhibitors in development and invasion of squamous cell carcinomas, as a basis for prognostication and therapeutic intervention in these tumors.

Carcinoma, Squamous Cell↗
PubMed1999

Flavobacterium psychrophilum in Baltic salmon Salmo salar brood fish and their offspring.

Baltic salmon brood fish were investigated for the presence of Flavobacterium psychrophilum in the kidney, spleen, brain and sexual products (ovarian fluid, unfertilised eggs and milt). Samples for bacteriology were taken at capture, when the fish were ascending their native river to spawn, and after a period of captivity in indoor pools, at stripping. During captivity, abnormal wiggling behaviour was recorded in some of the fish. Bacterial samples were taken to determine if F. psychrophilum had any role in the aetiology of the condition. Furthermore, the presence of F. psychrophilum on egg surfaces during incubation was investigated. F. psychrophilum was isolated from internal organs and/or sexual products in 7 out of 50 (14.0%) fish sampled at capture and 63 out of 272 (23.2%) fish sampled at stripping. The bacteria was isolated from either spleen or gonads in 2 out of 19 (10.5%) fish with abnormal wiggling behaviour but no bacteria was isolated from the brain. No F. psychrophilum was isolated from eggs at the eyed stage. Just before hatching, the bacterium was isolated from 5 out of 15 (33.3%) family groups. The present study shows that Baltic salmon brood fish are carriers of F. psychrophilum during their spawning migration. The presence of the bacteria in sexual products from both females and males indicates that transmission from the brood fish to the offspring should be considered an important route of infection.

Animals↗
PubMed1999

Collagenase-3 (MMP-13) is expressed by tumor cells in invasive vulvar squamous cell carcinomas.

Collagenase-3 (MMP-13) is a human matrix metalloproteinase specifically expressed by invading tumor cells in squamous cell carcinomas (SCCs) of the head and neck. Here, we have further elucidated the role of MMP-13 in tumor invasion by examining its expression in invasive malignant tumors of the female genital tract. Using in situ hybridization, expression of MMP-13 mRNA was detected in 9 of 12 vulvar SCCs, primarily in tumor cells, but not in intact vulvar epithelium, in cervical SCCs (n = 12), or in endometrial (n = 11) or ovarian adenocarcinomas (n = 8). MMP-13 expression was especially abundant in vulvar carcinomas showing metastasis to lymph nodes and was associated with expression of membrane type 1 MMP by tumor cells and gelatinase-A (MMP-2) by stromal cells, as detected by immunohistochemistry. MMP-13 mRNAs were detected in 9 of 11 cell lines established from vulvar carcinomas and in 4 of 6 cell lines from cervical carcinomas, whereas endometrial (n = 10) and ovarian (n = 9) carcinoma cell lines were negative for MMP-13 mRNA. No correlation was detected between MMP-13 expression and p53 gene mutations in vulvar SCC cell lines. However, MMP-13 expression was detected in 5 of 6 vulvar and cervical SCC cell lines harboring HPV 16 or 68 DNA. These results show that MMP-13 is specifically expressed by malignantly transformed squamous epithelial cells, including vulvar SCC cells, and appears to serve as a marker for their invasive capacity.

Adult↗
PubMed1998

Interactive effects of three structurally different polychlorinated biphenyls in a rat liver tumor promotion bioassay.

Interactive effects between the non-ortho-substituted 3,3', 4,4', 5-pentachlorobiphenyl (PCB126), the mono-ortho-substituted 2,3,3',4, 4'-pentachlorobiphenyl (PCB105), and the di-ortho-substituted 2,2',4, 4',5,5'-hexachlorobiphenyl (PCB153) were studied in an initiation/promotion bioassay. Female Sprague-Dawley rats were injected with 30 mg/kg ip of N-nitrosodiethylamine 24 h after partial hepatectomy. Five weeks later, weekly sc administrations of the three PCBs in 15 systematically selected dose combinations started. After 20 weeks of administration, the animals were killed and the livers were analyzed for areas expressing placental glutathione-S-transferase as a marker of preneoplastic foci. In addition, concentration of liver and kidney retinoids and plasma retinol was analyzed, as well as body and organ weights, plasma transaminases, and induction of hepatic cytochrome P450 1A1/2 (CYP1A1/2) and CYP2B1/2 activities. Data were analyzed with a multivariate method. At the doses applied in this study, weak antagonism was observed between PCB126 and PCB153 for effects on volume fraction of foci, number of foci/cm3, concentration of plasma retinol and liver retinoids, relative liver weight, and induction of CYP2B1/2 activity. Weak antagonism was also observed between PCB126 and PCB105 for effects on volume fraction of foci, number of foci/cm3, and plasma retinol concentration. No interactions other than pure additivity were observed between PCB105 and PCB153. Synergism was not observed within the dose ranges investigated in this study. Knowledge of interactive effects is important for risk assessment of environmental mixtures of dioxin-like compounds. Antagonism between congeners generally results in risk assessments that overestimate human risk. The significance to human risk assessment of the relatively weak antagonism observed in this study is however unclear, considering many other uncertainties involved in the toxic equivalency factor (TEF) concept. A change of the TEF concept for risk assessments of dioxin-like substances is not motivated based on the results of this study.

Animals↗
PubMed1998

Suprabasal expression of epidermal alpha 2 beta 1 and alpha 3 beta 1 integrins in skin treated with topical retinoic acid.

In normal adult human skin, expression of epidermal integrins is confined to keratinocytes in the basal layer. However, suprabasal expression of alpha 2, alpha 3 and beta 1 integrin subunits is noted in hyperproliferative epidermis in wound repair and psoriasis. In this study, we examined the effect of topical all-trans-retinoic acid (RA), known to induce epidermal hyperplasia, on expression of integrins in human epidermis. Immunostaining of vehicle-treated skin revealed expression of alpha 2, alpha 3 and beta 1, as well as alpha 6 and beta 4 integrin subunits entirely on basal keratinocytes. Topical application of RA (0.1%) for 2 weeks resulted in marked suprabasal expression of alpha 2, alpha 3 and beta 1 integrin subunits, whereas alpha 6 and beta 4 staining remained on basal keratinocytes. Staining for putative ligands of alpha 2 beta 1 and alpha 3 beta 1 integrins, i.e. type IV collagen, laminin-5 and fibronectin, was not detected in the epidermal layer in RA- or vehicle-treated skin. Treatment of HaCaT keratinocytes in culture with RA (1 mumol/L) enhanced alpha 2 and beta 1 mRNA abundance. Furthermore, RA slightly up-regulated the expression of alpha 2, alpha 3 and beta 1 integrin subunits on primary epidermal keratinocytes and HaCaT cells in culture with no effect on cell proliferation. These results provide evidence that RA-elicited epidermal hyperplasia is associated with aberrant suprabasal expression of alpha 2 beta 1 and alpha 3 beta 1 integrins, and that this also involves direct stimulation of keratinocyte integrin expression by RA.

Administration, Cutaneous↗
PubMed1998

Heat shock element architecture is an important determinant in the temperature and transactivation domain requirements for heat shock transcription factor.

The baker's yeast Saccharomyces cerevisiae possesses a single gene encoding heat shock transcription factor (HSF), which is required for the activation of genes that participate in stress protection as well as normal growth and viability. Yeast HSF (yHSF) contains two distinct transcriptional activation regions located at the amino and carboxyl termini. Activation of the yeast metallothionein gene, CUP1, depends on a nonconsensus heat shock element (HSE), occurs at higher temperatures than other heat shock-responsive genes, and is highly dependent on the carboxyl-terminal transactivation domain (CTA) of yHSF. The results described here show that the noncanonical (or gapped) spacing of GAA units in the CUP1 HSE (HSE1) functions to limit the magnitude of CUP1 transcriptional activation in response to heat and oxidative stress. The spacing in HSE1 modulates the dependence for transcriptional activation by both stresses on the yHSF CTA. Furthermore, a previously uncharacterized HSE in the CUP1 promoter, HSE2, modulates the magnitude of the transcriptional activation of CUP1, via HSE1, in response to stress. In vitro DNase I footprinting experiments suggest that the occupation of HSE2 by yHSF strongly influences the manner in which yHSF occupies HSE1. Limited proteolysis assays show that HSF adopts a distinct protease-sensitive conformation when bound to the CUP1 HSE1, providing evidence that the HSE influences DNA-bound HSF conformation. Together, these results suggest that CUP1 regulation is distinct from that of other classic heat shock genes through the interaction of yHSF with two nonconsensus HSEs. Consistent with this view, we have identified other gene targets of yHSF containing HSEs with sequence and spacing features similar to those of CUP1 HSE1 and show a correlation between the spacing of the GAA units and the relative dependence on the yHSF CTA.

Base Sequence↗
PubMed1998

Human TIMP-3 is expressed during fetal development, hair growth cycle, and cancer progression.

We studied the expression and regulation of TIMP-3, a recently cloned member of the tissue inhibitor of the metalloproteinase family, during human fetal development and in various human tissues, with emphasis on epithelial structures. Expression of TIMP-3 mRNA was detected by in situ hybridization in developing bone, kidney, and various mesenchymal structures. At 16 weeks of gestation, ectoderm-derived cells of hair germs expressed TIMP-3 mRNA, and beginning from the twentieth week consistent expression was detected in epithelial outer root sheath cells of growing hair follicles. In normal adult human skin, expression of TIMP-3 mRNA was limited to hair follicles, starting at the early anagen (growing) phase and vanishing at the catagen (regressing) phase. TIMP-3 mRNA was not detected in benign hair follicle-derived tumors but was present in tumor cells of infiltrative basal cell carcinomas and in surrounding stromal cells in squamous cell carcinomas. Human primary keratinocytes in culture expressed TIMP-3 mRNAs, the levels of which were upregulated by transforming growth factor-beta (TGF-beta), whereas interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) had no effect. Our results suggest a role for TIMP-3 in connective tissue remodeling during fetal development, hair growth cycle, and cancer progression.

Adult↗
PubMed1998

Collagenase-3 (matrix metalloproteinase-13) expression is induced in oral mucosal epithelium during chronic inflammation.

Increased proliferation of mucosal epithelium during inflammation is associated with degradation of subepithelial connective tissue matrix and local invasion of the epithelial cells. Here we have studied, whether collagenase-3 (MMP-13), a collagenolytic matrix metalloproteinase with an exceptionally wide substrate specificity, is expressed in the epithelium of chronically inflamed mucosa. Examination of human gingival tissue sections from subjects with chronic adult periodontitis with in situ hybridization revealed marked expression of MMP-13 in basal cells of some epithelial rete ridges expanding into connective tissue. Immunohistochemical staining demonstrated that these cells also expressed strongly laminin-5, suggesting that they are actively migrating cells. A strong signal for MMP-13 mRNA was occasionally also noted in the suprabasal epithelial cells facing the gingival pocket, whereas no collagenase-1 (MMP-1) mRNA was detected in any areas of the epithelium. MMP-13 expression was also detected in fibroblast-like cells associated with collagen fibers of the inflamed subepithelial connective tissue. In organ culture of human oral mucosa, MMP-13 mRNA expression was observed in epithelial cells growing into connective tissue of the specimens. Regulation of MMP-13 expression was examined in cultured normal nonkeratinizing epithelial cells isolated from porcine periodontal ligament. In these cells, MMP-13 expression at the mRNA and protein level was potently enhanced (up to sixfold) by tumor necrosis factor-alpha, transforming growth factor-beta(1), and transforming growth factor-alpha and by keratinocyte growth factor in the presence of heparin. In addition, plating periodontal ligament epithelial cells on type I collagen stimulated MMP-13 expression (sevenfold) as compared with cells grown on tissue culture plastic. The results of this study show, that expression of MMP-13 is specifically induced in undifferentiated epithelial cells during chronic inflammation due to exposure to cytokines and collagen. Thus, it is likely that MMP-13 expression is instrumental in the subepithelial collagenolysis and local invasion of the activated mucosal epithelium into the connective tissue.

Adolescent↗
PubMed1997

Collagenase-3 (MMP-13) is expressed by hypertrophic chondrocytes, periosteal cells, and osteoblasts during human fetal bone development.

Collagenase-3 (MMP-13) is a novel matrix metalloproteinase, the expression of which has so far only been documented in human breast carcinomas and osteoarthritic cartilage. In this study we have examined the expression of MMP-13 during human fetal development. Northern blot hybridizations revealed abundant expression of MMP-13 mRNAs in total RNA from fetal cartilage and calvaria at gestational age of 15 weeks. By in situ hybridization MMP-13 transcripts were detected in chondrocytes of hypertrophic cartilage in vertebrae of the spinal column and in the dorsal end of ribs undergoing ossification, as well as in osteoblasts and periosteal cells below the inner periosteal region of ossified ribs. In contrast, no expression of MMP-13 could be detected in osteoclasts. Furthermore, expression of MMP-13 mRNA was detected in osteoblasts and fibroblasts primarily on the inner side of calvarial bone of the skull at 16 weeks of gestation. Expression of MMP-13 mRNA by primary human fetal chondrocytes in culture was enhanced by transforming growth factor-beta (TGF-beta) and inhibited by bone morphogenetic protein-2 (BMP-2). No expression of MMP-13 mRNA could be noted in other fetal tissues, including the skin, lungs, neural tissue, muscle, and liver. These results suggest that MMP-13 plays an important role in the extracellular matrix remodeling during fetal bone development both via endochondral and intramembranous ossification.

Blotting, Northern↗
PubMed1997

Distinct populations of stromal cells express collagenase-3 (MMP-13) and collagenase-1 (MMP-1) in chronic ulcers but not in normally healing wounds.

Proteolysis is an intrinsic component of cutaneous wound repair and several matrix metalloproteinases have been shown to participate in various stages of this process. Therefore, we investigated the expression of a novel metalloproteinase, collagenase-3 (MMP-13), in normally healing cutaneous wounds and chronic venous ulcers. MMP-13 was expressed abundantly by fibroblasts deep in the chronic ulcer bed but was not detected in epidermis and all the acute wounds. The spatial expression of MMP-13 differed from that of collagenase-1 (MMP-1), which was prominently expressed by migrating keratinocytes and dermal cells located just beneath the wound surface. Northern blot hybridization did not reveal expression of MMP-13 by fibroblasts cultured on tissue culture plastic. In accordance with our in vivo findings, however, fibroblasts grown in a collagen gel produced MMP-13 mRNA abundantly. Our results suggest that MMP-13 can be induced in skin during wound repair after altered cell-matrix interactions. Although both MMP-1 and MMP-13 have the unique ability to degrade fibrillar collagens, their regulation and role during wound repair seem different. Collagenase-1 is critical for re-epithelialization, and MMP-13 most likely plays a role in the remodeling of collagenous matrix in chronic wounds.

Cell Count↗
PubMed1997

Human collagenase-3 is expressed in malignant squamous epithelium of the skin.

Co-expression of several members of the matrix metalloproteinase (MMP) family is a characteristic of human carcinomas. To investigate the role of the recently cloned collagenase-3 (MMP-13) in epidermal tumors, we studied samples representing malignant (basal and squamous cell carcinoma, Paget's disease), pre-malignant (Bowen's disease, solar keratosis), and benign (keratoacanthoma, seborrheic keratosis, linear epidermal nevus) tumors. Basal cell carcinomas expressed collagenase-3 mRNA in focal areas of keratinized cells, the squamous differentiation of which was confirmed by positive immunostaining for involucrin. Apoptosis was observed in central parts of these foci. In squamous cell carcinomas, collagenase-3 expression was detected at the epithelial tumor front and less frequently in the surrounding stromal cells. Collagenase-3 mRNA co-localized with immunostaining for laminin-5, an adhesion molecule suggested to participate in the migration of tumor cells. The pre-malignant and benign tumors were mostly negative for collagenase-3. Stromelysin-1, a potential activator of latent collagenases, was frequently expressed by stromal cells surrounding the malignant tumors, and the two MMPs occasionally co-localized in keratotic foci. Our results demonstrate that in basal cell carcinomas, expression of collagenase-3 is associated with terminal differentiation of epithelial cells. Furthermore, the gene is activated during skin carcinogenesis, and we suggest a role for collagenase-3 in degradation of the extracellular matrix associated with malignant epithelial growth.

Basement Membrane↗
PubMed1997

Collagenase 3 (matrix metalloproteinase 13) gene expression by HaCaT keratinocytes is enhanced by tumor necrosis factor alpha and transforming growth factor beta.

Collagenase-3 (matrix metalloproteinase 13; MMP-13) is a novel matrix metalloproteinase, the expression of which to date has only been detected in human breast carcinoma tissue and osteoarthritic cartilage. Here, we show that MMP-13 transcripts are expressed by human HaCaT keratinocytes but not by primary human epidermal keratinocytes. The levels of MMP-13 mRNAs in HaCaT cells were enhanced up to 130- and 45-fold by tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta), respectively. The maximal induction of MMP-13 mRNAs by TNF-alpha was noted after a 6-h incubation, whereas with TGF-beta, the maximal stimulation was observed after 24 h. The up-regulation of MMP-13 mRNA abundance by TNF-alpha and TGF-beta was dependent on protein synthesis and was prevented partially by dexamethasone and retinoic acid. Nuclear run-on assays demonstrated activation of MMP-13 gene transcription by TNF-alpha maximally at the 2-h time point and by TGF-beta after 12 h of treatment. Incubation of HaCaT keratinocytes with TNF-alpha and TGF-beta also increased production of proMMP-13 into the culture media, as detected by Western blotting. Our data indicate that the MMP-13 gene is expressed by transformed epidermal keratinocytes, suggesting a role for MMP-13 in the invasive capacity of human epidermal malignancies.

Blotting, Northern↗