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)

S100A8, S100A9, and S100A12, collectively known as myeloid-related proteins (MRPs), are highly expressed by the myeloid cell lineage and are found in the extracellular milieu during infections and inflammatory conditions. Recent data showed high levels of MRPs in the serum of HIV type 1 (HIV-1)-infected patients which correlated with disease progression and low CD4(+) counts. Therefore, we set out to investigate the effect of MRPs on HIV-1 replication. We observed a 4- to 5-fold induction of virus production in J1.1, a human T lymphoid cell line latently infected with HIV-1, following treatment with MRPs. Using luciferase-based reporter gene assays, we demonstrated that MRPs induce a dose- and time-dependent activation of the HIV-1 long terminal repeat promoter region that could be blocked by specific anti-MRP polyclonal Abs and by physical denaturation of these proteins. The MRP-mediated induction was acting through the HIV-1 enhancer sequence and was dependent upon NF-kappaB activity. These latter results were also confirmed by EMSA experiments conducted in Jurkat cells and freshly isolated PBMCs. In conclusion, we demonstrate that MRPs induce HIV-1 transcriptional activity and viral replication in infected CD4(+) T-lymphocytes at concentrations similar to those found in the serum of HIV-1-infected patients.
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PMID:HIV-1 transcription and virus production are both accentuated by the proinflammatory myeloid-related proteins in human CD4+ T lymphocytes. 1221 51

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

Cat scratch disease is an infectious disease usually caused by Bartonella henselae. Within 1-3 weeks after inoculation, patients typically develop regional self-limited lymphadenopathy. Lymph nodes reveal granulomas consisting of central necrosis, an inner rim of palisading macrophages, and an outer rim of lymphocytes and non-palisading macrophages. In animals, cat-scratch disease leads to an interferon-gamma (IFNgamma)-mediated T-helper 1 immune response, resulting in macrophage recruitment, stimulation, and thereby granuloma formation. The present study has sought to find in situ evidence for macrophage migration, activation, and cell death in human cat scratch disease. By non-radioactive in situ hybridization and immunohistochemistry on serial sections, it was demonstrated that IFNgamma+ T lymphocytes and S100A8+, S100A9+ macrophages embrace granulomas, which consisted of S100A8-, S100A9-, HLA-DR+, CD40+, TNFalpha+ macrophages. Combination of in situ end-labelling and immunofluorescence revealed large numbers of DNA-fragmented CD68+ cells with intact plasma membranes corresponding to apoptotic macrophages. On the basis of these data, it was hypothesized that in human cat scratch disease, S100A8+, S100A9+ macrophages continuously migrate to the granulomas. During this process, they may be activated by IFNgamma T-helper 1 lymphocytes and be differentiated to S100A8-, S100A9-sessile, HLA-DR+, CD40+ antigen-presenting, TNFalpha+ pro-inflammatory macrophages forming granulomas. In parallel, macrophages undergo apoptosis in the centre of granulomata, a phenomenon that may restrict the destructive potential of macrophages and contribute to self-limitation of cat scratch disease.
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PMID:Activation and apoptosis of macrophages in cat scratch disease. 1243 24

Precursor proteins of the acquired enamel pellicle derive from glandular and non-glandular secretions, which are components of whole saliva. The purpose of this investigation was to gain further insights into the characteristics of proteins in whole saliva and in vivo formed pellicle components. To maximize separation and resolution using only micro-amounts of protein, a two-dimensional gel electrophoresis system was employed. Protein samples from parotid secretion, submandibular/sublingual secretion, whole saliva, and pellicle were subjected to isoelectric focusing followed by SDS-PAGE. Selected protein spots were excised, subjected to "in-gel" trypsin digestion, and examined by mass spectrometry (MS). The data generated, including peptide maps and tandem MS spectra, were analyzed using protein data base searches. Components identified in whole saliva include cystatins (SA-III, SA, and SN), statherin, albumin, amylase, and calgranulin A. Components identified in pellicle included histatins, lysozyme, statherin, cytokeratins, and calgranulin B. The results showed that whole saliva and pellicle have more complex protein patterns than those of glandular secretions. There are some similarities and also distinct differences between the patterns of proteins present in whole saliva and pellicle. MS approaches allowed identification of not only well characterized salivary proteins but also novel proteins not previously identified in pellicle.
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PMID:Identification of protein components in human acquired enamel pellicle and whole saliva using novel proteomics approaches. 1244 93

Serial analysis of gene expression provides quantitative and comprehensive expression profiling in a given cell population. In our efforts to define the genes overexpressed in carcinoma of the stomach, we performed serial analysis of gene expression analyses on dissected neoplastic and normal gastric epithelia. We identified 91,334 expressed tags, including 26,633 that were unique. The 20 most up-regulated genes (P < 0.01) in gastric cancer (GC) compared with normal gastric epithelia included several keratins that are specific for epithelial cells such as keratin 6A, 13, and 17. Interestingly, five calcium-binding proteins (S100A2, S100A7, S100A8, S100A9, and S100A10) were overexpressed. Quantitative real-time PCR on primary GC samples demonstrated overexpression of S100A2 in 18 of 20 tumors (90%). The other calcium-binding proteins were overexpressed in 25-45% of the GC samples that we studied. Our results indicate that S100A proteins may be important for gastric tumorigenesis. Additional investigations are required to elucidate the biological role of calcium-binding proteins in cancer.
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PMID:Gastric cancers overexpress S100A calcium-binding proteins. 1246 Aug 93

S100A8 and S100A9, also called myeloid related protein (MRP) 8 and 14, are calcium-binding proteins highly expressed in neutrophils, in which they play a key role in the inflammatory progression. In this study, we looked at the expression of S100A8/A9 within gingiva from normal and Cyclosporin A (CsA)-induced overgrowth gingiva. In gingiva from the CsA group, several positive S100A8/A9 cells were seen within the connective tissue, whereas in normal gingiva very few positive S100A8/A9 cells were detected. These cells correspond either to activated macrophages or to neutrophils, reflecting the well-known gingival inflammatory status associated with the CsA-treated group. In addition, in both the normal and drug-treated group, the gingival epithelia appeared S100A8/A9 immunopositive. More specifically, S100A8/A9 appeared in the majority within the spino-cellular layer and located extracellularly within the desmosomes. In addition, S100A8/A9 also appeared sporadically intracellularly, located within the cytoplasm and the nuclei, reflecting S100A8/A9 translocations.
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PMID:S100A8 and S100A9 calcium-binding proteins: localization within normal and cyclosporin A-induced overgrowth gingiva. 1248 93

The S100A9 (MRP14) protein is abundantly expressed in myeloid cells and has been associated with various inflammatory diseases. The S100A9-deficient mice described here were viable, fertile, and generally of healthy appearance. The myelopoietic potential of the S100A9-null bone marrow was normal. S100A8, the heterodimerization partner of S100A9 was not detectable in peripheral blood cells, suggesting that even a deficiency in both S100A8 and S100A9 proteins was compatible with viable and mature neutrophils. Surprisingly, the invasion of S100A9-deficient leukocytes into the peritoneum and into the skin in vivo was indistinguishable from that in wild-type mice. However, stimulation of S100A9-deficient neutrophils with interleukin-8 in vitro failed to provoke an up-regulation of CD11b. Migration upon a chemotactic stimulus through an endothelial monolayer was markedly diminished in S100A9-deficient neutrophils. Attenuated chemokinesis of the S100A9-deficient neutrophils was observed by using a three-dimensional collagen matrix migration assay. The altered migratory behavior was associated with a microfilament system that was highly polarized in unstimulated S100A9-deficient neutrophils. Our data suggest that loss of the calcium-binding S100A9 protein reduces the responsiveness of the neutrophils upon chemoattractant stimuli at least in vitro. Alternative pathways for neutrophil emigration may be responsible for the lack of any effect in the two in vivo models we have investigated so far.
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PMID:Loss of S100A9 (MRP14) results in reduced interleukin-8-induced CD11b surface expression, a polarized microfilament system, and diminished responsiveness to chemoattractants in vitro. 1252 7

Protein complexes formed by S100A8 and S100A9 represent the only AA-binding capacity in the human neutrophilic cytosol and are involved in the intracellular arachidonic acid metabolism. The formation of S100A8/A9 protein complexes and the binding of calcium to the complexes are prerequisites for the specific binding of polyunsaturated fatty acids. The present study was undertaken to characterize the fatty acid binding site within the protein complex. Deletions at both termini and point mutations of different basic amino acids especially within the extended C-terminal tail of human S100A9 were introduced. The S100A9 mutant proteins were then analyzed with respect to protein-protein interaction (GST pull down-assay and yeast two-hybrid system) and functional properties (arachidonic acid and calcium binding). The data give strong evidence that the unique C-tail of S100A9 containing the three consecutive histidine residues (His103-His105) represents the region to which the fatty acid carboxy-group is bound to the protein complex. The localization of the AA-binding site within the unique C-tail of S100A9 correlates with the fact that fatty acid binding has not yet been reported for other S100 proteins.
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PMID:Evidence for the involvement of the unique C-tail of S100A9 in the binding of arachidonic acid to the heterocomplex S100A8/A9. 1255 26

S100A8 and S100A9 are small calcium-binding proteins that are highly expressed in neutrophil and monocyte cytosol and are found at high levels in the extracellular milieu during inflammatory conditions. Although reports have proposed a proinflammatory role for these proteins, their extracellular activity remains controversial. In this study, we report that S100A8, S100A9, and S100A8/A9 caused neutrophil chemotaxis at concentrations of 10(-12)-10(-9) M. S100A8, S100A9, and S100A8/A9 stimulated shedding of L-selectin, up-regulated and activated Mac-1, and induced neutrophil adhesion to fibrinogen in vitro. Neutralization with Ab showed that this adhesion was mediated by Mac-1. Neutrophil adhesion was also associated with an increase in intracellular calcium levels. However, neutrophil activation by S100A8, S100A9, and S100A8/A9 did not induce actin polymerization. Finally, injection of S100A8, S100A9, or S100A8/A9 into a murine air pouch model led to rapid, transient accumulation of neutrophils confirming their activities in vivo. These studies 1) show that S100A8, S100A9, and S100A8/A9 are potent stimulators of neutrophils and 2) strongly suggest that these proteins are involved in neutrophil migration to inflammatory sites.
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PMID:Proinflammatory activities of S100: proteins S100A8, S100A9, and S100A8/A9 induce neutrophil chemotaxis and adhesion. 1463 68

Neutrophils are rapidly recruited to sites of inflammation and are thereby at the forefront of the organism's defense against numerous attacks. As unspecific phagocytes, they belong to the so-called innate immunity. Two S100 proteins, namely S100A9 (MRP14) and S100A8 (MRP8), constitute roughly 40% of the cytosolic protein in these cells, implying by their pure abundance an important role in the effector functions of neutrophils. However, despite intense research in the past 15 years, the puzzle that may embed both molecules into the neutrophil/monocyte physiology is still incomplete. One reason might be the conformational variability the S100A9 and S100A8 molecules can adopt. They readily form hetero- and homodimeric, trimeric as well as tetrameric complexes, but they evidently do also exert specific functions as monomers. An ever-increasing body of information suggests that S100A9 plays a prominent role in leukocyte trafficking and arachidonic acid metabolism. In addition, elevated levels of S100A9 and S100A8 in body fluids of inflamed tissues strengthen the view that these molecules are important players in fighting inflammation. The aim of this review is to give an update on the current developments concerning the S100A9/S100A8 molecule in biology and medicine.
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PMID:S100A9/S100A8: Myeloid representatives of the S100 protein family as prominent players in innate immunity. 1264 5


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