Papers by Zsuzsanna Bata-csörgő
British Journal of Dermatology, 2016
What's already known about this topic? • In psoriasis the non-lesional skin already contains abno... more What's already known about this topic? • In psoriasis the non-lesional skin already contains abnormalities as base for the manifestation of the disease. • Fibronectin and its splice variant EDA + FN are essential extracellular matrix proteins influencing major cellular processes and they are abnormally expressed in psoriatic skin. • KGF is overexpressed in psoriatic lesional skin and contribute to keratinocyte hyperproliferation. What does this study add? • KGF and its receptor, FGFR2 is overexpressed in the psoriatic non-lesional skin. • KGF in an autocrine manner influences the regulation EDA + FN production in fibroblasts through MEK1 signaling. • Fibroblasts express the FGFR2-IIIc splice variant of FGFR2 receptor. • STAT1 negatively regulates FN and EDA + FN production in normal cultured fibroblasts, but not in fibroblasts, derived from psoriatic non-lesional skin. • STAT1 is active in healthy skin and psoriatic lesional skin, but not in non-lesional psoriatic skin. Summary Background Data indicate that in psoriasis abnormalities are already present in the nonlesional skin. TGFβ, KGF together with fibronectin and α5β1 integrin was suggested to play a crucial role in the pathogenesis of psoriasis by influencing inflammation and keratinocyte hyperproliferation. Objectives To investigate the expression of KGF, FGFR2, fibronectin (FN) and EDA + FN in healthy and non-lesional psoriatic skin and to study the effect of KGF on the regulation of FN and EDA + FN production by fibroblasts. Methods Healthy, non-lesional psoriatic skin and lesional psoriatic skin were immmunostained for α5 integrin, KGF, FGFR2, EDA + FN and STAT1. KGF treated cell cultures were analyzed for FN and EDA + FN mRNA and protein by real-time RT-PCR and flow cytometry respectively. The four major downstream signaling of KGF was investigated by blocking experiments using MEK1, AKT1/2, STAT1 and STAT3 inhibitors. Results The expression of α5 integrin, EDA + FN, KGF and its receptor FGFR2 is elevated in psoriatic non-lesional skin compared to healthy skin. KGF mildly induced EDA + FN, but not FN expression in healthy fibroblasts through MAPK signaling. Fibroblasts express the FGFR2-IIIc. STAT1 negatively regulates both FN and EDA + FN expressions in healthy fibroblasts and this regulation is compromised in fibroblasts derived from non-lesional psoriatic dermis. We detected active STAT1 in healthy and lesional skin, similar to a previous report, however, in the non-lesional skin STAT1 activation was absent in tissues far away from lesions. Conclusions The production of FN, EDA + FN by fibroblasts and the signaling of STAT1 is abnormally regulated in the psoriatic non-lesional skin.
Photochemistry and Photobiology, 2008
Melanocortin-1 receptor (MC1R) and agouti signaling protein (ASIP) play pivotal roles in the regu... more Melanocortin-1 receptor (MC1R) and agouti signaling protein (ASIP) play pivotal roles in the regulation of human pigmentation. We aimed to study whether single nucleotide polymorphisms (SNPs) of the MC1R and ASIP genes contribute to the pathogenesis of the polygenic pigment skin disorder, vitiligo. The PCR-amplified, full-length MC1R gene was studied with sequence analysis, and the 3' untranslated region (3' UTR) SNP of ASIP was detected using restriction fragment length polymorphism. The allele frequency of the ASIP SNP did not show any difference between the skin type, hair color and eye color-matched 97 vitiligo patients and the 59 healthy control individuals. As one of the MC1R polymorphisms showed significantly higher incidence among fair-skinned individuals (Fitzpatrick I+II, n=140) than among dark-skinned individuals (Fitzpatrick III+IV, n=90), both vitiligo patients and controls were divided into two groups and the frequency of the MC1R alleles was studied separately in fair-skinned and dark-skinned subgroups of diseased and healthy groups. C478T, one of the MC1R SNPs studied in 108 fair-skinned vitiligo patients and in 70 fair-skinned healthy control individuals, showed a significant difference (P=0.0262, odds ratio [95% confidence interval]=3.6 [0.0046-0.1003]) in allele frequency between the two groups: the allele frequency was higher in the control group, suggesting protection against vitiligo. Computer prediction of antigenicity has revealed that the Arg160Trp amino acid change caused by this SNP results in a decrease in antigenicity of the affected peptide epitope.
Microbes and Infection, 2009
p63 plays a pivotal role in the development and maintenance of stratified epithelial tissues. In ... more p63 plays a pivotal role in the development and maintenance of stratified epithelial tissues. In an effort to gain insight into the pathogenic mechanisms of skin infections caused by HSV-1 and HSV-2, we determined the patterns of p63 expression in primary keratinocytes and in the HaCaT cell line. The levels of DeltaNp63alpha and a 50kDa p73 isoform were decreased, Bax-alpha remained unaffected, while the expressions of the Bax-beta, TAp63gamma and a 44.5kDa p73 isoform were highly increased in both HSV-1-infected HaCaT cells and primary keratinocytes. In contrast, in response to HSV-2 infection the levels of DeltaNp63alpha, a 50kDa p73 isoform and a 44.5kDa p73 protein were decreased, Bax-alpha and TAp63gamma remained unaffected, while the expression of Bax-beta was slightly increased. The knockdown of TAp63 expression enhanced the viability of HSV-1-infected cells. Thus, HSV-1 and HSV-2 modulate the patterns of p63 and Bax expression in a serotype-specific manner. The dysregulated pattern of p63 expression observed in HSV-infected keratinocytes may comprise part of a mechanism by which these viruses perturb the functions of keratinocytes and lead to their demise.
Journal of the American Academy of Dermatology, 1999
Journal of Investigative Dermatology, 1995
Antigen-presenting (APC), suppressor T-cell-inducing macrophages infiltrate both human and murine... more Antigen-presenting (APC), suppressor T-cell-inducing macrophages infiltrate both human and murine epidermis after ultraviolet radiation (UVR) exposure. To determine their derivation, we prepared epidermal cell and dermal cell suspensions from human keratome biopsy specimens obtained from nonexposed skin and from UVB-irradiated sites (3 d after four times the minimal erythema dose). Simultaneous triple-marker flow cytometric analysis established the extended phenotype of macrophages infiltrating sunburned human epidermis (CD1a- CD1c- CD11b+ CD11c+ CD36+ Fc gamma RII+ DR+). This then enabled us to track dermal cells of this phenotype after UVR in relation to the heterogeneous DR+ populations in normal dermis. By both in situ immunohistology and cell suspension flow cytometry, UVR induced an expansion of bone marrow-derived DR+ cells in the perivasculature and sub-basement membrane zone of the papillary dermis. Despite an overall expansion of DR+ cells, the CD1a+ CD1c+ CD36- DR+ Langerhans-cell-like dendritic APC subset of dermal DR+ cells was depleted (p < 0.05), indicating that UVR-induced epidermal Langerhans cell loss (from 95% to 7% of DR+ epidermal cells) is not accounted for by Langerhans cell accumulation in the dermis. By contrast, UVR exposure induced a selective expansion of the dermal macrophage subset, which is phenotypically identical to the monocytic/macrophagic APCs that appear in the epidermis after UV injury (p < 0.01). Cell cycle analysis (to determine whether this expansion was accounted for entirely by infiltration) revealed no increase in the percentage of DR+ CD36+ UVR-exposed dermal cells in S/G2/M phase; however, the expanded DR+ CD36+ subset continued its already substantial level of proliferation unabated. Therefore, epidermal macrophages derive not only from transcapillary migration, but also from in situ proliferation of a dermal precursor. Taken together, these findings show that UVR creates an epidermal and dermal APC milieu which is dominated by monocytic/macrophagic cells, through depletion of cells of dentritic APC phenotype, and concomitant selective dermal expansion of a CD1a- CD1c- CD11b+ CD36+ Fc gamma RII+ DR+ (monocyte/macrophage) population.
Journal of Investigative Dermatology, 1998
Interferon-gamma (IFN-gamma) produced by lesional T cell clones is critical for the induction int... more Interferon-gamma (IFN-gamma) produced by lesional T cell clones is critical for the induction into G1 of the cell cycle by psoriatic keratinocyte stem cells; however, direct data demonstrating psoriatic lesional T cell subset IFN-gamma expression, and quantitation at a single cell level to calculate in vivo proportions, are lacking. In this study, using flow cytometry of freshly isolated normal and psoriatic lesional T cells from keratome biopsies, we found elevated CD3+, CD4+, and CD8+ T cells in all compartments of psoriatic skin, compared with normals. Using Brefeldin A to induce short-term intracellular accumulation of IFN-gamma in T cells capable of IFN-gamma production, we found that 90% of psoriatic patients have IFN-gamma-producing T cells at a greater proportion of their CD3+ cells than normals, with a mean of 16%+/-3%, as compared with 4%+/-2% in normal epidermis (p = 0.01). Expressed as density in the tissue, the IFN-gamma+ CD3+ cell number in psoriatic epidermis was 97+/-22 per mm2 surface area, as compared with 4.4+/-1.8 per mm2 of normal epidermis (p = 0.002). Thus, the total number of IFN-gamma+CD3+ T cells in the skin of a patient with 20% involvement is estimated to be 3.9 x 10(8). CD4+ and CD8+ IFN-gamma+ T cells were both elevated in psoriatic epidermis (p = 0.04 and p = 0.008, respectively) relative to normal skin. In the dermis, only 44% of patients demonstrated a higher percentage of IFN-gamma-producing T cells than did normals (p = 0.1), possibly indicating dilution, in some patients, by fresh infiltrating T cells. Interleukin-4 was not found by a combination of flow cytometry, reverse transcriptase-polymerase chain reaction, western blot, and immunoprecipitation. In conclusion, a significant portion of lesional T cells in psoriasis are IFN-gamma producing, without interleukin-4. The increased numbers of both IFN-gamma+CD4+ and IFN-gamma+CD8+ T cells indicate that both CD4+ and CD8+ IFN-gamma+ T cells are present in appropriate anatomic locations to sustain the lesional pathology.
Journal of Investigative Dermatology, 1995
An early cellular event in the development of psoriatic lesions is infiltration of target tissue ... more An early cellular event in the development of psoriatic lesions is infiltration of target tissue by macrophages and activated T lymphocytes. Lesional psoriatic skin contains activated memory T lymphocytes with production of mRNA for lymphokines such as interleukin-2, interferon-gamma, and tumor necrosis factor-alpha that is elevated relative to normal or uninvolved psoriatic skin. That the T-cell activation and cellular lymphokine production have a crucial role in the maintenance of epidermal hyperplasia in the psoriatic lesion is indicated by the beneficial effect of immunosuppressive agents in the treatment of psoriasis (cyclosporin A, FK506, anti-CD3, anti-CD4). A link between immune activation and psoriasis is also indicated by immunogenetic associations in this disease. Also, psoriatic keratinocytes appear to have been modulated by T-cell lymphokines in vivo, because they abnormally express molecules uniquely induced on keratinocytes by the T-cell product interferon-gamma. Indeed, T cells producing interferon-gamma have been cloned from psoriatic lesions, and they are able to induce keratinocyte class II major histocompatibility complex and intercellular adhesion molecule expression. These lesion-derived T-cell clones can induce growth of keratinocytes, and specifically lesional psoriatic T cells produce factors that induce increased keratinocyte colony formation, as well as increased cell cycle entry of the normally quiescent stem cell population. Interferon-gamma, although a growth inhibitor on its own, acts cooperatively with other T-cell-produced growth factors to cause keratinocyte growth induction. Furthermore, relative to normal stem cells, keratinocyte stem cells (beta 1 integrin+ K1/K10-) in psoriatic uninvolved epidermis are significantly hyperresponsive to the growth-stimulatory lymphokine milieu created by lesional T lymphocytes. Whether such abnormalities in responsiveness are associated with new genetic linkages reported in families of psoriasis patients is unknown. As the epidermis of lesional psoriatic skin can be demonstrated to produce elevated levels of factors that can further potentiate T-cell activation, a self-sustaining cycle can be constructed of T-cell recruitment, intralesional activation, release of factors that preferentially stimulate psoriatic epidermal stem cells to proliferate, and further epidermal potentiation of the T-cell-mediated lesions.
Journal of Experimental Medicine, 1993
In this study we define the proliferative compartments of in vivo human epidermis, using specific... more In this study we define the proliferative compartments of in vivo human epidermis, using specific antibodies related to cell differentiation (beta 1 and beta 4 integrins and K1/K10 differentiation keratins) and cell cycle (proliferating cell nuclear antigen [PCNA]) in combination with flow cytometric quantitation of the DNA content and optical characteristics of the cells. The beta 1 integrin (CD29) marked both of the potentially proliferative subsets in normal epidermis. One subset of normal epidermis is CD29+ K1/K10-, which was predominantly basal, and found to be comprised of slow cycling, small cells with primitive cytoplasmic organization. The vast majority (95.5%) of these cells were in a quiescent state (G0/early G1) as indicated by their lack of the cyclin, PCNA. The other proliferative subset of normal epidermis was CD29+ K1/K10+, which was suprabasal and occasional basal, highly proliferative, larger in size, and which exhibited a more complex cytoplasmic structure. Because early differentiation (K1/K10 expression) has begun in the CD29+ K1/K10+ subset, it is highly likely that they represent the proliferative population which is capable of transiently amplifying itself before terminal differentiation. Within lesional psoriatic epidermis, similar proliferative cell populations were present as in normal epidermis, and the hyperproliferative defect was localized to the beta 1 and beta 4 integrin+, K1/K10- populations, which in normal epidermis is basally located and quiescent with regard to cell cycle. In psoriatic epidermis, a six- to sevenfold increase in the number of cells in the S/G2+M phase of cell cycle was found among CD29+ K1/K10- cells (p < 0.05). Furthermore, all lesional K1/K10- cells showed high PCNA positivity, indicating that all these cells had been recently induced into cell cycle. By contrast, the proportion of cycling cells among lesional psoriatic CD29+ K1/K10+ keratinocytes was similar to normals. Anti-HLA-DR, CD45, and vimentin antibodies were used to concomitantly track the proliferative states of Langerhans cell, melanocyte, and infiltrating leukocyte populations. In normal epidermis, the cycling fractions (cells in S/G2/M phase) of these cells were similar to the CD29+K1/K10- keratinocytes, whereas in lesional epidermis their cycling pools were increased relative to normal, but not so much as the proliferative fractions of psoriatic CD29+ K1/K10- keratinocytes. These data demonstrate the use of simultaneous analysis of integrin expression, differentiation keratins, cyclin, cell cycle status, and optical characteristics of freshly isolated human epidermal cells. Such analysis allowed the physical identification and quantification of cy cling populations in normal human skin, and has enabled the precise location of the primary epidermal proliferative defect in psoriasis.
Journal of Clinical Investigation, 1995
Address correspondence to Zsuzsanna Bata-Csorgo, MD, Immunodermatology Unit, University of Michig... more Address correspondence to Zsuzsanna Bata-Csorgo, MD, Immunodermatology Unit, University of Michigan, R5548 Kresgel/Campus Box
Archives of Dermatological Research, 1998
Changes in the levels of IL-1 (IL-1α, IL-1 , and its receptor antagonist, IL-1RA) occur upon kera... more Changes in the levels of IL-1 (IL-1α, IL-1 , and its receptor antagonist, IL-1RA) occur upon keratinocyte differentiation in vitro and are associated in vivo with abnormal differentiated and hyperproliferative states of psoriatic keratinocytes. A flow cytometric procedure, capable of detecting changes in the intracellular levels of IL-1, was used to determine whether intracellular IL-1/IL-1RA levels in psoriatic and normal keratinocytes alter during in vivo differentiation and the cell cycle. Increases in the IL-1RA levels and IL-1α levels were observed as both normal and psoriatic keratinocytes differentiated from basal stem cells ( 1 integrin + , small size) into transient amplifying cells (TAC; 1 integrin + , large size). Upon further differentiation ( 1 integrin -, large size) both IL-1RA and IL-1α levels dropped. However, while psoriatic IL-1 levels increased as cells differentiated into TACs, little change occurred in the IL-1 levels of normal keratinocytes during differentiation. Changes in IL-1/IL-1RA levels were also detected as keratinocytes progressed through the cell cycle. Within the basal stem cell population of both normal and psoriatic keratinocytes, the IL-1α and IL-1RA levels increased between G0/G1 and S but not between S and G2/M. However, psoriatic basal keratinocyte IL-1 levels differed from those of normal keratinocytes by showing no increase between S and G2/M. The IL-1/IL-1RA levels of normal TAC increased throughout the cell cycle. However, in psoriatic TAC, a slight decrease in IL-1α and IL-1RA levels was observed between G0/G1 and S followed by a delayed increase between S and G2/M. IL-1 levels in psoriatic TAC varied little throughout the cell cycle. Thus, we were able to detect precisely the regulation of IL-1/IL-1RA intracellular levels during the keratinocyte cell cycle and differentiation, showing notably decreased IL-1 upregulation in psoriatic keratinocytes progressing through the cell cycle.
Annals of the Rheumatic Diseases, 2011
... However, TLR7 function in EORA was significantly different from that in GCA and closer to tha... more ... However, TLR7 function in EORA was significantly different from that in GCA and closer to that in HC. Furthermore, EORA was characterised by a different function of TLR5 (LÁ Rodríguez, M López-Hoyos, JC Alen, VM Martínez-Taboada, unpublished data). ...
Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology, 2015
It hasn't been clearly understood yet whether sensitization to antibiotics, the virus itself ... more It hasn't been clearly understood yet whether sensitization to antibiotics, the virus itself or transient loss of drug tolerance due to the virus, is responsible for the development of maculopapular exanthems following amoxicillin intake in patients with infectious mononucleosis. We aimed to examine whether sensitization to penicillin developed among patients with skin rash following amoxicillin treatment within infectious mononucleosis. Ten patients were investigated for drug sensitization by lymphocyte transformation test and six patients were further tested by prick-, intradermal and patch tests employing the penicillin's main antigens. Lymphocyte transformation test showed negative results with amoxicillin, while one patient had positive reaction to cefixime. Six patients with suspected sensitization to amoxicillin were then investigated by in vivo tests. Prick tests were negative in all six patients, but the intradermal tests showed positive reactions in four patients. ...
European journal of dermatology : EJD
Ulcus vulvae acutum Lipschütz or acute genital ulcer is a distinct clinical entity characterized ... more Ulcus vulvae acutum Lipschütz or acute genital ulcer is a distinct clinical entity characterized by sudden painful genital ulceration occurring mostly in young and virgin girls with malaise, fever and other systemic symptoms. This distressing syndrome is rare and may be presented to dermatologists, gynecologists or pediatricians. Its diagnosis and therapy can be challenging. We present two young female patients with ulcus vulvae acutum. The cause of the disease could not be confirmed in our patients, but, interestingly, both patients had partial IgA deficiency. In the last 100 years, after its first description by Lipschütz, many case reports and series have aimed to identify a specific cause of the disease, without success. These studies mainly focused on infectious agents as causative factors, however, in most cases connection with infection could not be confirmed. Our opinion is that the decreased level of IgA could be a possible explanation for the cause of this syndrome. With o...
PLoS ONE, 2011
In previous work we described a novel culture technique using a cholera toxin and PMA-free medium... more In previous work we described a novel culture technique using a cholera toxin and PMA-free medium (Mel-mix) for obtaining pure melanocyte cultures from human adult epidermis. In Mel-mix medium the cultured melanocytes are bipolar, unpigmented and highly proliferative. Further characterization of the cultured melanocytes revealed the disappearance of c-Kit and TRP-1 and induction of nestin expression, indicating that melanocytes dedifferentiated in this in vitro culture. Cholera toxin and PMA were able to induce c-Kit and TRP-1 protein expressions in the cells, reversing dedifferentiation. TRP-1 mRNA expression was induced in dedifferentiated melanocytes by UV-B irradiated keratinocyte supernatants, however direct UV-B irradiation of the cells resulted in further decrease of TRP-1 mRNA expression. These dedifferentiated, easily accessible cultured melanocytes provide a good model for studying melanocyte differentiation and possibly transdifferentiation. Because melanocytes in Mel-mix medium can be cultured with human serum as the only supplement, this culture system is also suitable for autologous cell transplantation.
Hungarian Medical Journal, 2008
1Department of Dermatology and Allergology,2Dermatological Research Group of the Hungarian Academ... more 1Department of Dermatology and Allergology,2Dermatological Research Group of the Hungarian Academy of Sciences, Szeged, 3Medical Microbiological and Immunobiological Institute, University of Szeged, Szeged, 4Plant Biological Institute, Szeged Biological Center of the Hungarian ...
International Wound Journal, 2014
Seminars in Cancer Biology, 2008
Accumulating data on non-protein-coding transcripts suggest that besides the regulatory machinery... more Accumulating data on non-protein-coding transcripts suggest that besides the regulatory machinery driven by proteins, another yet enigmatic regulatory network of RNA molecules operates and has considerable impact on cell functions. Moreover, deregulation of these non-coding RNAs (ncRNAs) has been documented in several human diseases suggesting that they may significantly contribute to their pathogenesis. This review summarizes our present knowledge on the role of the so-called mRNA-like ncRNAs in the complexity of multicellular organisms. We provide some examples to show how these mRNA-like non-coding RNAs have been discovered, how their cellular functions and role in the pathogenesis of human diseases have been revealed.
Photochemistry and Photobiology, 2008
Melanocortin-1 receptor (MC1R) and agouti signaling protein (ASIP) play pivotal roles in the regu... more Melanocortin-1 receptor (MC1R) and agouti signaling protein (ASIP) play pivotal roles in the regulation of human pigmentation. We aimed to study whether single nucleotide polymorphisms (SNPs) of the MC1R and ASIP genes contribute to the pathogenesis of the polygenic pigment skin disorder, vitiligo. The PCR-amplified, full-length MC1R gene was studied with sequence analysis, and the 3¢ untranslated region (3¢ UTR) SNP of ASIP was detected using restriction fragment length polymorphism. The allele frequency of the ASIP SNP did not show any difference between the skin type, hair color and eye color-matched 97 vitiligo patients and the 59 healthy control individuals. As one of the MC1R polymorphisms showed significantly higher incidence among fair-skinned individuals (Fitzpatrick I + II, n = 140) than among dark-skinned individuals (Fitzpatrick III + IV, n = 90), both vitiligo patients and controls were divided into two groups and the frequency of the MC1R alleles was studied separately in fair-skinned and dark-skinned subgroups of diseased and healthy groups. C478T, one of the MC1R SNPs studied in 108 fair-skinned vitiligo patients and in 70 fair-skinned healthy control individuals, showed a significant difference (P = 0.0262, odds ratio [95% confidence interval] = 3.6 [0.0046-0.1003]) in allele frequency between the two groups: the allele frequency was higher in the control group, suggesting protection against vitiligo. Computer prediction of antigenicity has revealed that the Arg160Trp amino acid change caused by this SNP results in a decrease in antigenicity of the affected peptide epitope.
Journal of Photochemistry and Photobiology B: Biology, 2011
Photodynamic therapy is based on the selective accumulation of a photosensitizer in tumors, follo... more Photodynamic therapy is based on the selective accumulation of a photosensitizer in tumors, followed by destruction of the target tissue by a light source. Protoporphyrin IX, a well-known photosensitizer, was recently reported as an endogenous substrate for the multidrug transporter ABCG2. We investigated the role of ABCG2 protein in the porphyrin extrusion ability of keratinocytes, with regard to the impact of the specific inhibition of ABCG2 by a non-toxic fumitremorgin C analog, Ko-134, on photodynamic therapy efficacy. We studied the level of porphyrin accumulation in response to delta-aminolevulinic acid pretreatment in proliferating and highly differentiated HaCaT keratinocytes. An in vitro model of photodynamic therapy on HaCaT cells was established with a therapeutically approved narrow-bandwidth red-light source. The porphyrin extrusion ability of HaCaT cells proved to correlate with their ABCG2 expression which was higher in proliferating cells than in differentiated cells. Moreover, the specific inhibition of ABCG2 by Ko-134 enhanced the sensitivity of keratinocytes to photodynamic therapy in vitro. These results suggest that ABCG2 may serve as a target molecule via which to improve the photodynamic therapy of skin lesions: its inhibition by the non-toxic Ko-134 is a promising therapeutic modality.
Journal of Investigative Dermatology, 2001
Humans express three distinct collagenases, MMP-1, , that initiate degradation of ®brillar type I... more Humans express three distinct collagenases, MMP-1, , that initiate degradation of ®brillar type I collagen. We have previously reported that ultraviolet irradiation causes increased expression of MMP-1, but not MMP-13, in keratinocytes and ®broblasts in human skin in vivo. We report here that ultraviolet irradiation increases expression of MMP-8 in human skin in vivo. Western analysis revealed that levels of the full-length, 85 kDa proenzyme form of MMP-8 increased signi®cantly within 8 h post ultraviolet irradiation (2 minimal erythema doses). Increased full-length MMP-8 protein was associated with in®ltration into the skin of neutrophils, which are the major cell type that expresses MMP-8. Immuno¯uorescence revealed coexpression of MMP-8 and neutrophil elastase, a marker for neutrophils. Immunohistology demonstrated MMP-8 expression in neutrophils in the papillary dermis between 4 and 8 h post ultraviolet irradiation, and in the epidermis at 24 h post radiation. MMP-8 mRNA expression was not detected in nonirradiated or ultraviolet-irradiated human skin, indicating that increased MMP-8 following ultraviolet irradiation resulted from preexisting MMP-8 protein in in®ltrating neutrophils. Pretreatment of skin with the glucocorticoid clobetasol, but not alltrans retinoic acid, signi®cantly blocked ultravioletinduced increases in MMP-8 protein levels, and neutrophil in®ltration. In contrast, all-trans retinoic acid and clobetasol were equally effective in blocking ultraviolet induction of MMP-1 and degradation of collagen in human skin in vivo. Taken together, these data demonstrate that ultraviolet irradiation increases MMP-8 protein, which exists predominantly in a latent form within neutrophils, in human skin in vivo. Although ultraviolet irradiation induces both MMP-1 and MMP-8, ultraviolet-induced collagen degradation is initiated primarily by MMP-1, with little, if any, contribution by MMP-8. Key words: collagen/ glucocorticoid/neutrophil collagenase/retinoid acid. J Invest Dermatol 117: 219±226, 2001
Uploads
Papers by Zsuzsanna Bata-csörgő