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Abstract: Transcriptional regulation in mammalian cells is driven by a complex interplay of multiple transcription factors that respond to signals from either external or internal stimuli. A single transcription factor can control expression of distinct sets of target genes, dependent on its state of post-translational modifications, interacting partner proteins, and the chromatin environment of the cellular genome. Furthermore, many transcription factors can act as either transcriptional repressors or activators, depending on promoter and cellular contexts [Alvarez, M., Rhodes, S.J., Bidwell, J.P., 2003. Context-dependent transcription: all politics is local. Gene 313, 43-57]. Even in this light, the versatility of LSF (Late SV40 Factor) is remarkable. A hallmark of LSF is its unusual DNA binding domain, as evidenced both by lack of homology to any other established DNA-binding domains and by its DNA recognition sequence. Although a dimer in solution, LSF requires additional multimerization with itself or partner proteins in order to interact with DNA. Transcriptionally, LSF can function as an activator or a repressor. It is a direct target of an increasing number of signal transduction pathways. Biologically, LSF plays roles in cell cycle progression and cell survival, as well as in cell lineage-specific functions, shown most strikingly to date in hematopoietic lineages. This review discusses how the unique aspects of LSF DNA-binding activity may make it particularly susceptible to regulation by signal transduction pathways and may relate to its distinct biological roles. We present current progress in elucidation of both tissue-specific and more universal cellular roles of LSF. Finally, we discuss suggestive data linking LSF to signaling by the amyloid precursor protein and to Alzheimer''s disease, as well as to the regulation of latency of the human immunodeficiency virus (HIV). [Copyright &y& Elsevier]

Carp subjected to daily handling stress were much more susceptible to Trypanoplasma borreli infection than control fish. In a search for the cellular mechanisms involved, it was observed that cortisol suppressed T. borreli-induced expression of interleukin-1β, tumor necrosis factor-α, serum amyloid A and inducible nitric oxide synthase. An NF-κB-inhibitor could replicate cortisol-induced apoptosis of activated peripheral blood leukocytes. In contrast, although this NF-κB-inhibitor induced apoptosis of neutrophilic granulocytes, cortisol prevented apoptosis of these cells, suggesting the latter process to be NF-κB-independent. Carp leukocytes, upon induction of apoptosis, exhibit a number of sequential metabolic alterations. First, the mitochondrial transmembrane potential (ΔΨm) is disrupted and glutathione levels are depleted, followed by exposure of phosphatidylserine on the outer cell membrane. In vitro, cortisol could inhibit NO production induced by low concentrations of lipopolysaccharide (LPS), but remarkably, enhanced NO production induced by high concentrations of LPS. However, no differences in NO production were observed in stressed versus non-stressed infected carp. [Copyright &y& Elsevier]

We have previously characterized the first invertebrate homolog of serum amyloid A (SAA) proteins in the sea cucumber Holothuria glaberrima, where its expression is associated with intestinal regeneration, suggesting a possible involvement of SAA proteins in intestinal morphogenesis. Here we show that bacterial lipopolysaccharides (LPS) trigger a coelomocyte-mediated immune response in H. glaberrima, inducing an approximately threefold increase in coelomocyte phagocytic activity. Furthermore, LPS induces an approximately fourfold increase in SAA mRNA levels in non-regenerating intestines. These results show that in H. glaberrima, LPS act as an immune activator and that SAA expression can be modulated by immune-associated processes. [Copyright &y& Elsevier]

Formyl peptide receptors are G-protein-coupled, seven-transmembrane domain receptors originally identified in leukocytes. Ligands for this class of receptors include the chemotactic peptide fMet-Leu-Phe, lipoxin A4, serum amyloid A and β-amyloid peptides. The formyl peptide receptor gene family contains three members in human and six members in mouse. By screening a mouse genomic library, we isolated two novel genes that were provisionally named Fpr-rs6 and Fpr-rs7. They encode putative seven-transmembrane domain proteins of 339 and 338 residues, respectively, and share between them 94% amino acid identity. The predicted amino acid sequences of Fpr-rs6 and Fpr-rs7 are 53–74% identical to other mouse formyl peptide receptors. The transcript of Fpr-rs6 is found in brain, spleen and skeletal muscle, and at high level in testis. The Fpr-rs7 transcript is more widely expressed in heart, liver, lung, spleen, smooth muscle and pancreas. Our data suggest that the expression of Fpr-rs6 and Fpr-rs7 is differentially regulated in mouse despite their high sequence homology. [Copyright &y& Elsevier]

The innate arm of the immune system responds to inflammatory stimuli by the activation of phagocytes, and by altered levels of several plasma proteins. These changes in plasma proteins comprise a major component of the acute phase response, which is thought to be an adaptive response that contributes to regaining homeostasis after tissue injury or infection. In this study, rainbow trout (Oncorhynchus mykiss) were injected with a variety of potential inflammatory agents, and changes in the concentrations of plasma proteins were sought in polyacrylamide gels in which plasma proteins had been electrophoresed. Bacteria, viruses and yeast all induced changes in plasma protein profiles. Increases were first evident 2 days after injections, and most were evident within 1 week. The greatest number of changes occurred after injection with aVibrio bacterin emulsified in Freund''s incomplete adjuvant. While some proteins increased and others decreased following several treatments, other proteins changed only in response to injections of viruses or viral proteins, and others changed in response to bacterial components. Some proteins that increased after yeast injection decreased after injection of viral components. The partial amino acid sequence of one increased protein identified it as haptoglobin. [Copyright &y& Elsevier]

We studied the value of serum amyloid A (SAA), a first-class acute-phase protein, as a marker for coronary heart disease (CHD) in a middle-aged male population. In a working population of 16 307 men (age, 35–59 years), 446 cases had a history of CHD or prominent Q:QS waves on electrocardiogram. For each case, two matched controls were investigated. SAA, measured by immunonephelometry, was correlated with other acute-phase proteins, cardiovascular risk factors, and infectious serology markers. SAA concentrations were significantly higher in the cases than in controls (P<0.05) and correlated with serum C-reactive protein (CRP) (r=0.61), plasma fibrinogen (r=0.39), serum haptoglobin (r=0.26), and body mass index (r=0.13) (P<0.001). Serum CRP is a better marker for CHD than SAA, which showed discriminative power only in a univariate model comparing highest versus lowest tertile (odds ratio, 1.39; 95% confidence interval, 1.03–1.87). Neither SAA nor other acute-phase proteins correlated with Chlamydia pneumoniae immunoglobulin (Ig)G, Helicobacter pylori IgG and IgA, and cytomegalovirus IgG. In conclusion, although SAA has a discriminative value for CHD, serum CRP is to be preferred as a first-class acute-phase reactant for detection of the disease. [Copyright &y& Elsevier]