Archivum immunologiae et therapiae experimentalis
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Arch. Immunol. Ther. Exp. (Warsz.) · Jan 2007
ReviewPeroxisome proliferator-activated receptor gamma (PPAR gamma) and sepsis.
This review describes the role of the nuclear hormone receptor PPARgamma as a double-edged sword in sepsis. On the one hand, PPARgamma inhibits pro-inflammatory gene expression, predominantly by scavenging transcription factors and their cofactors, thus preventing them from binding to their cognate binding sites in the promoters of target genes. The expressions of the affected genes, such as those for inducible nitric oxide synthase, TNF-alpha, or IL-1beta, are repressed. ⋯ Under these circumstances, a second infection cannot be adequately answered, thus causing septic shock and multi-organ dysfunction syndrome. Therefore the role of PPARgamma is still ambiguous. Particularly its role in initiating apoptosis awaits further clarification to finally elucidate its impact on sepsis development.
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Arch. Immunol. Ther. Exp. (Warsz.) · Jul 2006
Comparative StudyModifier effect of the Toll-like receptor 4 D299G polymorphism in children with cystic fibrosis.
Clinical phenotype varies amongst cystic fibrosis (CF) patients with identical CF transmembrane regulator (CFTR) genotype, suggesting genetic modifiers exist. One potential modifier is the Toll-like receptor 4 (TLR4) gene. TLR4 binds lipopolysaccharide (LPS), a constituent of Pseudomonas aeruginosa (PA), activating innate immunity and promoting inflammation. TLR4 polymorphisms are associated with LPS-hyporesponsiveness and may be protective in CF due to decreased inflammation. ⋯ Potential reasons for absence of modifier effect include the basolateral location of TLR4 receptors on respiratory epithelium, or because inflammatory response to PA in the CF airway is so overwhelming that even a blunted response (as suggested for the 299G allele) results in increased inflammation and lung damage.
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Arch. Immunol. Ther. Exp. (Warsz.) · Mar 2006
ReviewMonoclonal and bispecific antibodies as novel therapeutics.
Gene amplification, over-expression, and mutation of growth factors, or the receptors themselves, causes increased signaling through receptor kinases, which has been implicated in many human cancers and is associated with poor prognosis. Tumor growth has been shown to be decreased by interrupting this process of extensive growth factor-mediated signaling by directly targeting either the surface receptor or the ligand and thereby preventing cell survival and promoting apoptosis. Monoclonal antibodies have long been eyed as a potential new class of therapeutics targeting cancer and other diseases. ⋯ Further within this section, cancer-specific, site-specific, or signaling pathway-specific therapies are discussed in detail. Among other antibody-based therapeutic products, we discuss: Avastin (bevacizumab), CG76030, Theragyn (pemtumomab), daclizumab (Zenapax), TriAb, MDX-210, Herceptin (trastuzumab), panitumumab (ABX-EGF), mastuzimab (EMD-72000), Erbitux (certuximab, IMC225), Panorex (edrecolomab), STI571, CeaVac, Campath (alemtuizumab), Mylotarg (gemtuzumab, ozogamicin), and many others. The end of the review deliberates upon potential problems associated with cancer immunotherapy.
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Arch. Immunol. Ther. Exp. (Warsz.) · Mar 2006
ReviewP-selectin mediates adhesion of leukocytes, platelets, and cancer cells in inflammation, thrombosis, and cancer growth and metastasis.
Stimulated endothelial cells and activated platelets express P-selectin (CD62P), a member of the selectin family of cell adhesion molecules, which interacts with P-selectin glycoprotein ligand-1 (PSGL-1, CD162) for leukocyte rolling on stimulated endothelial cells and heterotypic aggregation of activated platelets onto leukocytes. Cross-linking of PSGL-1 by P-selectin also primes leukocytes intracellularly for cytokine and chemoattractant-induced beta2-integrin activation for firm adhesion of leukocytes. Furthermore, P-selectin mediates heterotypic aggregation of activated platelets to cancer cells and adhesion of cancer cells to stimulated endothelial cells. Here we provide a comprehensive summary of the functional roles and the biological importance of P-selectin-mediated cell adhesive interactions in the pathogeneses of inflammation, thrombosis, and the growth and metastasis of cancers.
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Arch. Immunol. Ther. Exp. (Warsz.) · Jul 2005
ReviewMonocyte-related immunopathologies in trauma patients.
Mechanical trauma is one of the most important causes of morbidity in the developed world. The response of the immune system to mechanical insult is of paramount importance for the patient's recovery. Shortly after trauma, the indiscriminate systemic inflammatory response syndrome (SIRS) is mediated by circulating monocytes (M Øs) and other innate immunity components. ⋯ This precisely regulated process of immune system activation in response to trauma can be easily deviated, resulting in multiorgan failure (MOF) and increased mortality. Excessive activation of inflammatory M Øs in the SIRS phase, premature or exorbitant CARS, a predominance of macrophages (Macs) in the blood stream and peripheral tissues, as well as a depletion of dendritic cells are often seen in trauma patients and contribute to the development of MOF. Here we explore several mechanisms of pathological MØ; activation in patients with severe mechanical traumatic injury without accompanying sepsis.