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 monoclonal antibody F12, raised against epidermal cells from a psoriatic lesion, decorated antigens highly expressed in psoriatic epidermis and in cultured normal human keratinocytes. In normal human skin, F12 reacted only with follicular keratinocytes. Characterization of the immunoprecipitated antigens by two-dimensional gel electrophoresis revealed their identity with calgranulin A and B. A semiquantitative study with various established epithelial cell lines demonstrated that the expression of calgranulin A and B in hyperproliferative keratinocytes correlates with their potential to undergo terminal differentiation. In epidermis reconstructed in vitro, the antigen expression was stimulated by retinoids and suppressed under vitamin A starvation.
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PMID:Differential expression of calgranulin A and B in various epithelial cell lines and reconstructed epidermis. 143 Dec 28

Since macrophage activation can now be studied at a global level using modern microarray and proteomic analyses, discovery of novel macrophage activation genes is inevitable and important for understanding HIV-associated dementia (HAD). We isolated two different types of primary human macrophages: microglia and monocyte-derived macrophages (MDM) from brain tissue and whole blood, respectively. The microarray analysis of differentially regulated macrophage activation genes reported here supports our previous assertions that the mixed glia (MIX) cultured in starvation conditions (DMEM alone) are a non-activated, or "quiescent", tissue culture model for studying macrophage activation in the brain. Transcript levels from these quiescent cultures provided a background level of gene expression and allowed for the identification of upregulated macrophage activation genes in the MIX brain cultures upon treatment with an array of soluble activation factors: serum components, cytokines, and growth factors. We found that 914 genes in the MIX cultures and 734 genes in the MDM cultures had a greater than twofold increase in expression. We discovered 180 genes with expression that was increased more than twofold in both culture types. Microarray-specific statistical analyses were performed to complement fold change analysis: significance analysis of microarrays (SAM) and Partek Pro. In the MIX cultures, we detected over a 100-fold increase in IL-1beta and TIMP1 transcription; Caspase 9, S100A8 and 9, MMP12, IL-8, monocyte chemotactic protein 1 (MCP1), MRC-1, and IL-6 were also upregulated. Activation of starved MDM cultures resulted in fewer upregulated genes compared to MIX cultures. Genes upregulated in both MIX and MDM included CCL2 (MCP1), CCL7, CXCL5, TNFSF14, kinases, and phosphatases. These microarray data may provide leads for identifying previously unknown neurotoxins, disease biomarkers, and pathways responsible for the neuronal apoptosis observed in HAD and for the eventual identification of therapeutic targets and treatments.
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PMID:Microarray analysis of activated mixed glial (microglia) and monocyte-derived macrophage gene expression. 1557 77

Most microbial pathogens have a metabolic iron requirement, necessitating the acquisition of this nutrient in the host. In response to pathogen invasion, the human host limits iron availability. Although canonical examples of nutritional immunity are host strategies that limit pathogen access to Fe(III), little is known about how the host restricts access to another biologically relevant oxidation state of this metal, Fe(II). This redox species is prevalent at certain infection sites and is utilized by bacteria during chronic infection, suggesting that Fe(II) withholding by the host may be an effective but unrecognized form of nutritional immunity. Here, we report that human calprotectin (CP; S100A8/S100A9 or MRP8/MRP14 heterooligomer) inhibits iron uptake and induces an iron starvation response in Pseudomonas aeruginosa cells by sequestering Fe(II) at its unusual His6 site. Moreover, under aerobic conditions in which the Fe(III) oxidation state is favored, Fe(II) withholding by CP was enabled by (i) its ability to stabilize this redox state in solution and (ii) the production and secretion of redox-active, P. aeruginosa-produced phenazines, which reduce Fe(III) to Fe(II). Analyses of the interplay between P. aeruginosa secondary metabolites and CP indicated that Fe(II) withholding alters P. aeruginosa physiology and expression of virulence traits. Lastly, examination of the effect of CP on cell-associated metal levels in diverse human pathogens revealed that CP inhibits iron uptake by several bacterial species under aerobic conditions. This work implicates CP-mediated Fe(II) sequestration as a component of nutritional immunity in both aerobic and anaerobic milieus during P. aeruginosa infection.
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PMID:The human innate immune protein calprotectin induces iron starvation responses in Pseudomonas aeruginosa. 3062 35

Calprotectin (CP) is a versatile player in the metal-withholding innate immune response, a process termed "nutritional immunity." CP is a heterooligomer of the polypeptides S100A8 and S100A9 and houses two transition-metal-binding sites at its S100A8/S100A9 heterodimer interface. During infection, CP is released from host cells and sequesters "bioavailable" transition metal ions in the extracellular space, thereby preventing microbial acquisition of these essential nutrients. For many years, the role of CP in nutritional immunity was interpreted in the contexts of Mn(II) and Zn(II) limitation, but recent work has broadened our understanding of its contributions to this process. We uncovered that CP provides a form of nutritional immunity that has previously received little attention: the battle between host and microbe for ferrous iron (Fe(II)). In this Account, we present our current understanding of Fe(II) coordination by CP and its role in Fe(II) withholding as well as considerations for future discovery. Nutritional immunity was first described in the context of host-microbe competition for ferric iron (Fe(III)). The battle for Fe(II) has received comparably little attention because the abundance of Fe(II) at infection sites and the importance of Fe(II) acquisition for microbial pathogenesis were recognized only recently. Several years ago, we discovered that human CP sequesters Fe(II) at its His6 site with subpicomolar affinity and thus hypothesized that it provides a means for Fe(II) limitation by the host during microbial infection. Fe(II) coordination by CP is unprecedented in biology because of its novel hexahistidine coordination sphere and its high-affinity binding, which surpasses that of other known Fe(II)-binding proteins. CP is also capable of shifting the Fe redox equilibrium by stabilizing Fe(II) in aerobic solution and can thereby sequester Fe in both reducing and nonreducing environments. These coordination chemistry studies allowed us to hypothesize that CP provides a means for Fe(II) limitation by the host during microbial infection. While investigating this putative Fe(II)-sequestering function, we discovered that CP withholds Fe from diverse bacterial pathogens. Recent studies by our lab and others of the bacterial pathogens Pseudomonas aeruginosa and Acinetobacter baumannii have shown that, by preventing sufficient Fe acquisition, CP induces Fe starvation responses in these organisms. As a result, CP affects bacterial virulence and metabolism. We also elucidated a complex interplay between CP and secondary metabolites produced by P. aeruginosa during the competition for Fe. Our work provides a foundation for understanding how CP affects Fe homeostasis during microbial infection. We believe that understanding how bacterial physiology is altered when challenged with Fe(II) withholding by CP will likely reveal crucial determinants of bacterial survival within the host.
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PMID:Exploring Iron Withholding by the Innate Immune Protein Human Calprotectin. 3138 1