Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05109 (S100A8)
 1,212 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of the heterodimeric complex of the calcium-binding proteins MRP-8 and MRP-14 was investigated in various inflammatory dermatoses using immunohistochemical staining with the monoclonal antibody 27E10. In addition to the inflammatory infiltrate, a positive staining was repeatedly found in the involved epidermis from patients with lichen planus, lupus erythematosus and psoriasis vulgaris, but not in normal skin epidermis and/or in epidermis from leucocytoclastic vasculitis patients. The keratinocytic expression of the 27E10 antigen was dissimilar to that of the MHC class-II molecules and the adhesion molecule ICAM-1. These data indicate that the 27E10 antigen is a distinct activation marker of inflammatory keratinocytes and may have proinflammatory properties.
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PMID:Epidermal expression of the calcium binding surface antigen 27E10 in inflammatory skin diseases. 128 18

Analysis by means of two-dimensional (2D) gel electrophoresis of the protein patterns of normal and psoriatic unfractionated non-cultured keratinocytes has revealed a few low-molecular-weight proteins that are highly up-regulated in psoriatic skin. These include psoriasin; calgranulin B, also known as MRP 14, L1, or calprotectin; calgranulin A or MRP 8; and cystatin A or stefin A. Here, we have cloned and sequenced the cDNA (clone 1592) encoding a new member of this group of low-molecular-weight proteins [isoelectric focusing (IEF) SSP 3007 in the keratinocyte 2D gel protein database] that we have termed PA-FABP (psoriasis-associated fatty acid-binding protein). The deduced sequence predicted a protein with molecular weight of 15,164 daltons and a calculated pI of 6.96, values that are close to those recorded in the keratinocyte 2D gel protein database. The protein comigrated with PA-FABP as determined by 2D gel analysis of [35S]-methionine-labeled proteins expressed by transformed human amnion (AMA) cells transfected with clone 1592 using the vaccinia virus expression system and reacted with a rabbit polyclonal antibody raised against 2D gel purified PA-FABP. Structural analysis of the amino acid sequence revealed 48%, 52%, and 56% identity to known low-molecular-weight fatty acid-binding proteins belonging to the FABP family. Northern blot analysis showed that PA-FABP mRNA is indeed highly up-regulated in psoriatic keratinocytes. The transcript is present in human cell lines of epithelial and lymphoid (Molt 4) origin but cannot be detected in normal or SV40 transformed MRC-5 fibroblasts. 2D gel protein analysis of normal primary keratinocytes cultured for at least 8 d under conditions that promoted incomplete terminal differentiation [serum-free keratinocyte (SFK) medium supplemented with epidermal growth factor (EGF), pituitary extract, and 10% fetal calf serum] revealed a strong up-regulation of PA-FABP, psoriasin, calgranulins A and B, and a few other proteins that are highly expressed in psoriatic skin. The levels of these proteins exceeded by far those observed in non-cultured normal keratinocytes implying that the cultured cells have followed an altered pattern of differentiation that resembles--at least in part--that of non-cultured psoriatic keratinocytes. The implications of these results for the study of psoriasis are discussed.
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PMID:Molecular cloning and expression of a novel keratinocyte protein (psoriasis-associated fatty acid-binding protein [PA-FABP]) that is highly up-regulated in psoriatic skin and that shares similarity to fatty acid-binding proteins. 151 66

Migration inhibitory factor-related protein 8 (MRP8) and MRP14, two S-100-like Ca(2+)-binding proteins, have been described in cells of the epithelial lineage where they are either expressed constitutively (e.g. by mucosal squamous epithelium) or induced during disease (e.g. in keratinocytes during the course of psoriasis). Their biological function, however, is not yet clear. Recent studies have provided evidence that S-100-like proteins may interact with cytoskeletal components; we have therefore studied the biochemical properties and subcellular distribution of MRP8 and MRP14 in epithelial cells. TR146 human squamous carcinoma cells, which were found to express MRP8 and MRP14 in Northern and Western blot studies, were chosen for analysis. Cross-linking experiments using bis(sulphosuccinimidyl)suberate followed by SDS/PAGE and Western blot analysis revealed formation of heteromeric MRP8-MRP14 complexes. On subjecting TR146 cell lysates to two-dimensional gel electrophoresis and Western blotting, four distinct MRP14 isoforms could be identified resembling those described earlier in macrophages. A differential centrifugation technique revealed a Ca(2+)-dependent translocation of MRP8-MRP14 from the cytoplasm to the membrane and the Nonidet P40-insoluble cytoskeletal fraction. Double-label immunofluorescence microscopy of Ca2+ ionophore A23187-stimulated TR146 cells and cytochalasin B and demecolcine cytoskeleton disruption studies identified these structures as keratin intermediate filaments. Ca(2+)-dependent binding of MRP8-MRP14 to keratin filaments was additionally confirmed by an in vitro binding assay. In conclusion, our data suggest that MRP8 and MRP14 may be involved in Ca(2+)-dependent reorganization of cytoskeletal filaments in epithelial cells, which could be of importance for events associated with differentiation and inflammatory activation.
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PMID:Increase of calcium levels in epithelial cells induces translocation of calcium-binding proteins migration inhibitory factor-related protein 8 (MRP8) and MRP14 to keratin intermediate filaments. 754 68

Retinoids down-regulate the expression of metalloproteinases, cytokines, and other genes involved in cell proliferation and inflammation. Tazarotene (AGN 190168), a retinoic acid receptor (RAR)-specific retinoid, is effective in the treatment of psoriasis, a hyperproliferative and inflammatory skin disease. Because negative regulation of genes appears to be important in the antiproliferative and antiinflammatory action of retinoids, we studied the down-regulation of genes in skin raft cultures by this antipsoriatic retinoid. By subtraction hybridization, we found that migration inhibitory factor-related protein (MRP-8) and skin-derived anti-leukoproteinase (SKALP) are down-regulated by AGN 190168. MRP-8 and SKALP are overexpressed in psoriatic lesions as compared to the normal epidermis, and they are markers of hyperproliferative keratinocyte differentiation. We also show that MRP-8 expression is retinoid inhibitable in cultured keratinocytes induced to differentiate with 10% serum or IFN-gamma, and that MRP-8 is inhibited by RAR but not by retinoid X receptor-specific retinoids in a dose-dependent manner. Finally, MRP-8, SKALP, and the previously characterized differentiation marker, transglutaminase I, are all down-regulated in vivo in psoriatic lesions after treatment with AGN 190168 in comparison to placebo. Taken together, these data suggest that these markers may be down-regulated by tazarotene in psoriasis through direct action on keratinocyte gene expression rather than by an overall tazarotene effect on lesional therapeutic status.
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PMID:Negative regulation of two hyperproliferative keratinocyte differentiation markers by a retinoic acid receptor-specific retinoid: insight into the mechanism of retinoid action in psoriasis. 895 47

The effect of French maritime pine bark extract (PBE) on the gene expression profile of HaCaT human keratinocytes was studied using high density filter arrays. The expression profile of both control and PBE-treated cells was determined. Interestingly, PBE was shown to downregulate both calgranulin A and B genes which are known to be upregulated in psoriasis and various dermatoses. Thus, PBE could be considered in human dermatoses.
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PMID:From ancient remedies to modern therapeutics: pine bark uses in skin disorders revisited. 1118 May 29

Psoriasis is an inflammatory skin disorder characterised by keratinocyte hyper-proliferation and altered differentiation. To date, linkage analyses have identified at least seven distinct disease susceptibility regions (PSORS1-7). The PSORS4 locus was mapped by our group to chromosome 1q21, within the Epidermal Differentiation Complex. This cluster contains 13 genes encoding S100 calcium-binding proteins, some of which ( S100A7, S100A8 and S100A9) are known to be up-regulated in individual patient keratinocytes. In this study, we analysed S100 gene expression in psoriatic individuals from families characterised by linkage studies. We first selected individuals from two large pedigrees, one of which was linked to the 1q21 locus, whereas the other was unlinked to that region. We studied the expression of 12 S100 genes, by semi-quantitative RT-PCR and Northern blot. These analyses demonstrated up-regulation of S100A8, S100A9 and, to a lesser extent, S100A7 and S100A12, only in the 1q21 linked family. We subsequently analysed S100A7, S100A8, S100 A9 and S100 A12 in three additional samples and were able to confirm S100A8/ S100A9-specific over-expression in 1q-linked pedigrees. Thus, our data provide preliminary evidence for a locus-specific molecular mechanism underlying psoriasis susceptibility.
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PMID:Evidence for differential S100 gene over-expression in psoriatic patients from genetically heterogeneous pedigrees. 1238 71

S100 proteins are calcium-activated signaling proteins that interact with target proteins to modulate biological processes. Our present studies compare the level of expression, and cellular localization of S100A7, S100A8, S100A9, S100A10, and S100A11 in normal and psoriatic epidermis. S100A7 and S100A11 are present in the basal and spinous layers in normal epidermis. These proteins appear in the nucleus and cytoplasm in basal cells but are associated with the plasma membrane in spinous cells. S100A10 is present in basal and spinous cells, in the cytoplasm, and is associated with the plasma membrane. S100A8 and S100A9 are absent or are expressed at minimal levels in normal epidermis. In involved psoriatic tissue, S100A10 and S100A11 levels remain unchanged, whereas, S100A7, S100A8, and S100A9 are markedly overexpressed. The pattern of expression and subcellular localization of S100A7 is similar in normal and psoriatic tissue. S100A8 and S100A9 are strongly expressed in the basal and spinous layers in psoriasis-involved tissue. In addition, we demonstrate that S100A7, S100A10, and S100A11 are incorporated into detergent and reducing agent-resistant multimers, suggesting that they are in vivo transglutaminase substrates. S100A8 and S100A9 did not form these larger complexes. These results indicate that S100 proteins localize to the plasma membrane in differentiated keratinocytes, suggesting a role in regulating calcium-dependent, membrane-associated events. These studies also indicate, as reported previously, that S100A7, S100A8, and S100A9 expression is markedly altered in psoriasis, suggesting a role for these proteins in disease pathogenesis.
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PMID:S100 protein subcellular localization during epidermal differentiation and psoriasis. 1270 15

Cutaneous exposure to ultraviolet (UV) A (320-400 nm) results in the formation of damaging reactive oxygen intermediates, which are implicated as mediators of DNA damage, apoptosis, and photoaging. S100A8 is a low-molecular-weight calcium-binding protein, highly sensitive to oxidation. In this study, UVA-induced S100A8 expression by keratinocytes was investigated. UVA (50-100 kJ per m2) strongly induced S100A8 in differentiated keratinocytes in the epidermis of BALB/c mice. Similarly, S100A8 mRNA and monomeric protein were significantly upregulated in PAM212 cells (a murine keratinocyte cell line) in response to 10 kJ per m2 UVA 24 h after irradiation. Although S100A9 associates with S100A8 in neutrophils and abnormally differentiated keratinocytes (human psoriasis), in this study it was not coinduced with keratinocyte S100A8. Dorsal application of 4-hydroxy-tempo (a superoxide dismutase-mimicking agent) to mice concentration-dependently reduced UVA-induced S100A8 expression. Incubation of PAM212 cells with superoxide dismutase and catalase during UVA irradiation also abrogated S100A8 induction. These results suggest that UVA-induced S100A8 is expressed by keratinocytes in response to generation of reactive oxygen intermediates.
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PMID:S100A8 induction in keratinocytes by ultraviolet A irradiation is dependent on reactive oxygen intermediates. 1470 22

The S100 proteins comprise a family of 21 low molecular weight (9-13 kDa) proteins that are characterized by the presence of two calcium-binding EF-hand motifs. Fourteen S100 protein genes are located within the epidermal differentiation complex on human chromosome 1q21 and 13 S100 proteins (S100A2, S100A3, S100A4, S100A6, S100A7, S100A8, S100A9, S100A10, S100A11, S100A12, S100A15, S100B, and S100P) are expressed in normal and/or diseased epidermis. S100 proteins exist in cells as anti-parallel hetero- and homodimers and upon calcium binding interact with target proteins to regulate cell function. S100 proteins are of interest as mediators of calcium-associated signal transduction and undergo changes in subcellular distribution in response to extracellular stimuli. They also function as chemotactic agents and may play a role in the pathogenesis of epidermal disease, as selected S100 proteins are markedly overexpressed in psoriasis, wound healing, skin cancer, inflammation, cellular stress, and other epidermal states.
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PMID:S100 proteins in the epidermis. 1519 38

Psoriasis is a frequent, inflammatory disease of skin and joints with considerable morbidity. Here we report that in psoriatic lesions, epidermal keratinocytes have decreased expression of JunB, a gene localized in the psoriasis susceptibility region PSORS6. Likewise, inducible epidermal deletion of JunB and its functional companion c-Jun in adult mice leads (within two weeks) to a phenotype resembling the histological and molecular hallmarks of psoriasis, including arthritic lesions. In contrast to the skin phenotype, the development of arthritic lesions requires T and B cells and signalling through tumour necrosis factor receptor 1 (TNFR1). Prior to the disease onset, two chemotactic proteins (S100A8 and S100A9) previously mapped to the psoriasis susceptibility region PSORS4, are strongly induced in mutant keratinocytes in vivo and in vitro. We propose that the abrogation of JunB/activator protein 1 (AP-1) in keratinocytes triggers chemokine/cytokine expression, which recruits neutrophils and macrophages to the epidermis thereby contributing to the phenotypic changes observed in psoriasis. Thus, these data support the hypothesis that epidermal alterations are sufficient to initiate both skin lesions and arthritis in psoriasis.
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PMID:Psoriasis-like skin disease and arthritis caused by inducible epidermal deletion of Jun proteins. 1616 48


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