Abstract:
BACKGROUND:Due to their immunosuppressive therapy, organtransplant recipients (OTRs) exhibit a high incidence for the development of cutaneous squamous cell carcinoma (cSCC). Randomized studies of kidney-transplanted patients indicate a significant lower susceptibility for cSCC among patients receiving the mTOR-inhibitor Sirolimus, compared to patients without mTOR-regimen. The exact mechanism, how mTOR inhibition affects keratinocyte carcinogenesis remains unclear. OBJECTIVE:Our aim was to investigate the impact of Sirolimus on the expression level of the oncogene ATF3, which is involved in the development and progression of cSCC. METHODS:We incubated human keratinocytes, cSSC cell lines and 3D skin equivalents with Sirolimus, exposed the cells to calcineurin inhibitors (CNI) and UVA-radiation and measured the expression level of ATF3 by real-time PCR and western blot. RESULTS:We show that Sirolimus downregulates the expression of ATF3 induced by cyclosporine or cyclosporine plus UV-radiation in keratinocytes. In line with this we demonstrate a decrease in ATF3 expression, by incubating 3D skin equivalents with Sirolimus prior to cyclosporine and UV-light. However, Sirolimus has no significant impact on the ATF3 expression levels of cyclosporine stimulated cSCC cell lines. CONCLUSION:Taken together, our study demonstrates that Sirolimus downregulates the CNI or UV-induced ATF3 expression in human keratinocytes, which could be a potential molecular mechanism how Sirolimus reduces cSCC in OTRs. The lack of ATF3 suppression by Sirolimus in cSCC cell lines fits to observations from clinical studies which demonstrated a clinical benefit from the switch to a mTOR-regimen in patients with low tumor burden in early stage of disease.
journal_name
J Dermatol Scijournal_title
Journal of dermatological scienceauthors
Schaper-Gerhardt K,Walter A,Schmitz-Rode C,Satzger I,Gutzmer Rdoi
10.1016/j.jdermsci.2018.08.013subject
Has Abstractpub_date
2018-11-01 00:00:00pages
172-180issue
2eissn
0923-1811issn
1873-569Xpii
S0923-1811(18)30324-4journal_volume
92pub_type
杂志文章abstract:BACKGROUND:Th17 is a newly identified effector T cell lineage which plays a central role in many human inflammatory diseases and experimental animal models. Epicutaneous sensitization with a protein antigen has been proven to induce a Th2-predominant immune response and lead to development of atopic diseases in a murin...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2008.12.011
更新日期:2009-06-01 00:00:00
abstract::The effect of cyclosporin A (CsA) on suppressor T cells (Ts) was evaluated by in vitro incubation with afferent-phase Ts (Ts-aff) and efferent-phase Ts (Ts-eff). 2,4-Dinitro-1-fluorobenzene (DNFB) and hen egg-white lysozyme (HEL) were used as antigens. Both Ts-aff and Ts-eff were resistant to high- and low-dose CsA tr...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/0923-1811(90)90218-3
更新日期:1990-03-01 00:00:00
abstract:BACKGROUND:Netherton syndrome (NS) is a rare but severe type of ichthyosis characterized by atopy, allergies, and potentially lethal skin overdesquamation associated with highly elevated proteolytic activities in LEKTI-deficient epidermis. NS symptoms are recapitulated in Spink5-/- mouse where the gene encoding Lekti h...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2019.06.004
更新日期:2019-07-01 00:00:00
abstract::The influence of dibutyril cyclic AMP (dbcAMP) on the gene expression of matrix metalloproteinases (MMP)-1, MMP-2, MMP-3, tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2 was investigated in human skin fibroblasts by northern analyses. The treatment of dbcAMP increased MMP-1 and MMP-3 mRNA levels but decrea...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/s0923-1811(97)00035-2
更新日期:1997-08-01 00:00:00
abstract:BACKGROUND:Retinoic acid (RA) enhances skin-lightening capabilities of hydroquinone (HQ), at least in part, by facilitating desquamation which leads to increase penetration of HQ. The desquamation also affects skin irritation levels. The mechanism of RA-induced desquamation, however, has not been completely explored an...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2017.03.023
更新日期:2017-08-01 00:00:00
abstract:BACKGROUND:Mammalian epidermis has two diffusion barriers, the stratum corneum (SC) and tight junctions (TJs). We reported previously that a single living cell layer exists between the SC and TJ-forming keratinocytes in mice; however, the exact location of the TJ barrier in human epidermis has not been defined. OBJECT...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2013.04.021
更新日期:2013-08-01 00:00:00
abstract:BACKGROUND:Netherton syndrome (NS, MIM 256500) is a potential live threatening autosomal-recessive skin disorder clinically characterized by the trias of congenital erythroderma, hair shaft anomalies and atopic diathesis. It is caused by mutations in the gene SPINK5 resulting in a deficiency of its processed protein na...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2010.12.004
更新日期:2011-03-01 00:00:00
abstract::The usefulness of the Yucatan miniature pig as a screen for skin dipigmenting activity by topical application was evaluated with standard compounds. This is a naturally occurring breed of swine with light brown to dark brown skin that is relatively hairless. The skin morphology, including the pattern of pigment distri...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/0923-1811(91)90007-k
更新日期:1991-12-01 00:00:00
abstract:BACKGROUND:Sarcoidosis is a systemic granulomatous disease characterized by the combination of Th1 and Th17 responses. Recently, several arguments have suggested a potential involvement of B cells as well as T cells in the pathogenesis of sarcoidosis. Follicular helper CD4+ T (TFH) cells are specialized in interacting ...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2020.02.002
更新日期:2020-03-01 00:00:00
abstract::Epithelial-mesenchymal transition (EMT) plays important roles not only in the morphogenesis but also in wound repair, tissue fibrosis and cancer progression. Recently, regulatory mechanism of this process has been elaborately elucidated. EMT can be a new therapeutic target for treating skin ulcer, fibrosing alopecia, ...
journal_title:Journal of dermatological science
pub_type: 杂志文章,评审
doi:10.1016/j.jdermsci.2010.11.015
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:Evidence suggests anti-inflammatory effects of glucosamine (GS) on inflammatory diseases. COX-2 is an enzyme to produce prostaglandins. MMPs are the family of matrix metalloproteinases degradable of ECM. Excess expression of COX-2 or MMPs involves in skin inflammation. OBJECTIVE:We evaluated whether GS-HCl ...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2009.06.017
更新日期:2009-10-01 00:00:00
abstract:BACKGROUND:O-linked β-N-acetylglucosamine (O-GlcNAc) modification is one of the posttranslational modification, emerging as an important regulatory mechanism in various cellular events. OBJECTIVE:We attempted to investigate whether O-GlcNAcylation is involved in keratinocyte differentiation. METHODS:Immunohistochemis...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2014.04.010
更新日期:2014-07-01 00:00:00
abstract:BACKGROUND:Psoriasis is a common multi-factorial skin disease, in which gene-gene and gene-environment interactions may affect the onset, manifestation and clinical course. OBJECTIVE:To investigate the underlying gene-environment interaction among several established susceptibility genes, cigarette smoking and alcohol...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2013.02.006
更新日期:2013-05-01 00:00:00
abstract:BACKGROUND:Using JAK inhibitors to inhibit cytokine signaling is presumed to be a possible means of treating skin inflammatory disorders such as contact dermatitis. OBJECTIVE:To clarify the action site of JAK inhibitors in skin inflammatory disorders. METHODS:We analyzed the mechanism of action of the JAK inhibitor J...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2016.09.007
更新日期:2016-12-01 00:00:00
abstract::Psoriatic skin lesions contain HLA-DR positive T lymphocytes, and other activation antigens, which suggest that the T cells may be producing lymphokines. Gamma interferon is produced by activated T cells, and its presence in psoriasis has been inferred by the lesional keratinocyte expression of 3 gamma interferon-indu...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/0923-1811(91)90019-t
更新日期:1991-03-01 00:00:00
abstract::Over the last decade, animal models of atopic dermatitis (AD) have received increasing attention. They include NC/Nga mice, a hapten-induced mouse model, and transgenic and knockout mouse models. Although the pathogenesis of skin inflammation elicited in these models and that in AD are not quite the same, it is pertin...
journal_title:Journal of dermatological science
pub_type: 杂志文章,评审
doi:10.1016/j.jdermsci.2004.02.013
更新日期:2004-10-01 00:00:00
abstract::This study reports on the isolation and characterization of a cDNA clone, regulated by androgen transcriptionally, in male Golden hamsters' flank organs. Previous studies have reported on the cloning of an androgen-dependent gene, FAR-17a, from the same hamster organ. After castration, the FAR-17c transcription rate d...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/0923-1811(94)00357-k
更新日期:1995-03-01 00:00:00
abstract:BACKGROUND:Several inhibitor of apoptosis proteins (IAPs) are cleaved during apoptosis. Studies of the melanoma-associated IAP (ML-IAP) Livin, using recombinant molecules, have implicated both caspases 3/7 and the serine protease Omi/HtrA2 in its proteolytic cleavage. OBJECTIVE:To characterize the apoptotic cleavage o...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2006.05.007
更新日期:2006-09-01 00:00:00
abstract:BACKGROUND:Atopic dermatitis (AD) is a highly pruritic, chronic inflammatory skin disease associated with hyperreactivity to environmental triggers. Among those, outdoor air pollutants such as particulate matter (PM) have been reported to aggravate pre-existing AD. However, underlying mechanisms of air pollution-induce...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2018.02.012
更新日期:2018-06-01 00:00:00
abstract::Dermatitis herpetiformis is characterised by granular IgA precipitates in the papillary dermis. In contrast to other autoimmune blistering diseases, where tissue-deposited and circulating autoantibodies recognise the same target within the skin, in dermatitis herpetiformis a serum IgA reacting with a component of the ...
journal_title:Journal of dermatological science
pub_type: 杂志文章,评审
doi:10.1016/j.jdermsci.2003.11.004
更新日期:2004-04-01 00:00:00
abstract:BACKGROUND:Skin lesions commonly affect AIDS patients. The pathogenesis of certain dermatologic disorders primarily associated to HIV-1 is unclear, and better forms of therapy for these conditions need to be discovered. Transgenic animal models represent a novel approach for the study of these disorders and for the que...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2008.08.015
更新日期:2009-02-01 00:00:00
abstract:BACKGROUND:Psoriasis is a systemic inflammatory disease with dramatic responses to TNF-α inhibitors. TNF-α is mainly produced by macrophages. However, how macrophage polarization contributes to psoriasis remains unknown. OBJECTIVE:We aimed to investigate the molecular mechanisms of macrophage polarization in psoriasis...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2018.05.009
更新日期:2018-09-01 00:00:00
abstract::Large numbers of pigmented melanocytes are located in human hair follicles, predominantly around the dermal papillae, and the number of melanocytes and the melanogenic activity of the hair follicles are closely related to the hair cycle. We found that cultured human dermal papilla cells secreted a melanocyte chemoattr...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/s0923-1811(01)00145-1
更新日期:2002-01-01 00:00:00
abstract::The effects of Werner's syndrome (WS) fibroblast-conditioned medium on cell proliferation and collagen production of normal fibroblasts were studied using four WS fibroblast strains. The conditioned medium from the WS fibroblasts brought about activation of normal fibroblast proliferation, whereas, that from late pass...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/0923-1811(94)90097-3
更新日期:1994-06-01 00:00:00
abstract::Crystalloid inclusion bodies (CIB) of the endothelial cells (EC) were investigated in blood vessels of human fetal skin and the umbilical cord by electron- and immunoelectron microscopy. They were found in up to 15% of the investigated EC in various types of vessels. Their sizes ranged from 0.2 microns to 0.6 microns ...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/0923-1811(91)90020-x
更新日期:1991-03-01 00:00:00
abstract::DS-Nh (DS Nh/+) mice spontaneously develop dermatitis when they are housed in a conventional environment. In this study, we analyzed the clinical and histopathological features of dermatitis in DS-Nh mice, which is characterized by erythema, edema, and erosion on the face, neck, chest and flexor surfaces of their fore...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/s0923-1811(02)00070-1
更新日期:2002-11-01 00:00:00
abstract::Survival and extracellular matrix gene expression were studied by viable cell count assay and Northern transfer analysis to compare the sensitivity of normal skin and keloid fibroblasts towards x-irradiation. As the dosage of radiation increased, the numbers of viable cells in irradiated groups were remarkably decreas...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/0923-1811(94)90318-2
更新日期:1994-08-01 00:00:00
abstract:BACKGROUND:The exact mechanism of the inflammatory changes occurring during the development of Behçet's disease (BD) remains unclear. OBJECTIVE:We investigated the role of classical (M1) and alternative (M2) activation of macrophages in a herpes simplex virus (HSV)-induced BD mouse model. METHODS:The classical vs. al...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2013.11.001
更新日期:2014-03-01 00:00:00
abstract:BACKGROUND:We sometimes encounter difficulties in assessing the severity of pediatric atopic dermatitis (AD) using currently available biomarkers such as thymus and activation-regulated chemokine (TARC) due to the higher baseline values in non-AD children. Recent case control studies have indicated the usefulness of sq...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2019.07.005
更新日期:2019-08-01 00:00:00
abstract:BACKGROUND:Ultraviolet (UV) irradiation is the main contributing factor for skin aging. UV irradiation induces epigenetic changes in skin. It increases the activity of histone acetylases (HATs) but decreases that of histone deacetylases (HDACs). OBJECTIVE:We aimed to investigate alterations in all classes of HDACs and...
journal_title:Journal of dermatological science
pub_type: 杂志文章
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更新日期:2020-12-03 00:00:00