J774 macrophage-like cell line cytokine and chemokine patterns are modulated by Francisella tularensis LVS strain infection.

Mutual interactions were investigated between intracellular parasitic bacterium Francisella tularensis (F.t.; highly virulent bacterium responsible for tularemia, replicating within the host macrophages) and murine macrophage-like cell line J774. Recombinant murine lymphokine INF-gamma and/or LPS derived from E. coli were determined to stimulate in vitro antimicrobial activity of macrophage-like J774 cell line against the live vaccine strain (LVS) of F.t. through their ability to produce proinflammatory cytokines and chemokines. F.t. infection up-regulated IL-12 p40 production and down-regulated TNF-alpha production by stimulated macrophages; on the other hand, F.t. infection did not affect the production of IL-8, IL-6, MCP-5, and RANTES by stimulated macrophages. This showed that F.t. infection modulates the cytokine synthesis by J774 macrophage cell line.

Neutrophil apoptosis by Fas/FasL: harmful or advantageous in cardiac surgery?

Polymorphonuclear leukocytes or neutrophils are the main executors of cellular death, both in septic inflammation during bacterial infection and in sterile inflammation during trauma or surgery. Whereas in septic inflammation neutrophils perform a useful function to fortify the host's defense against infection, in sterile inflammation, by contrast, they contribute to unwelcome tissue damage. Regardless of the situation, activated neutrophils exhibit a prolonged lifespan and delayed apoptotic death which, under normal conditions, is a prerequisite for their natural renewal. Traditionally, delayed neutrophil apoptosis was considered to promote trauma or surgical injury. According to the results of recent studies, however surprising they may appear, the reverse might be in keeping with what happens IN VIVO. Apoptotic signaling in neutrophils could, by contrast, contribute to intrinsic protection of the host's tissues. This review article, aimed preferentially but not exclusively at the cardiac surgeon, presents some new information in support of this viewpoint, which fits in with our own observations.

[Mucosal immunity with emphasis on urinary tract immunity and diabetes]. / Imunita na sliznicích se zretelem na sliznici urogenitálního traktu a diabetes.

Protective immune response in urinary tract is frequently impaired in patients with diabetes. Immunity in this mucosal compartment displays unique characteristics; e.g. absence of physiological microflora and lack of mucus. Pathogens are identified by the PRR receptors expressed on both epithelial and immune cells. Inflammatory response characterised by the acumulation ofgranulocytes is followed. Both protective and harm characteristics of inflammatory response are inseparable linked and delineated by gene polymorphisms in PRR receptors.

[Cardiac surgery operations and their influence on serum level of antiinflammatory cytokine interleukin-10]. / Kardiochirurgické operace a jejich vliv na sérovou hladinu protizánetového cytokinu interleukinu-10.

BACKGROUND: Cardiac surgical operation is followed by the development of inflammatory reaction. This reaction is regulated in many ways including the production of antiinflammatory cytokines such as IL-10 to avoid potentially harmful effects of inflammation. METHODS AND RESULTS: We compared serum levels of cytokines IL-10, IL-6, and IL-13 in the group of patients undergoing cardiac surgical operation using either cardiopulmonary bypass (CPB, n=17) or surged on the beating heart (n=17). We found significant elevation in the serum level of IL-10 during surgery with the peak immediately after finishing surgery in CPB patients and at the first postoperative day in non-CPB patients, respectively. There is statistically significantly higher level of IL-10 in CPB patients in comparison with non-CPB patients at the end of surgery. Serum level of IL-6 is elevated in both groups during surgery reaching maximum immediately after surgery in CPB patients and at the first postoperative day in patients without CPB, respectively. The serum levels of IL-13 are only nonsignificantly changed during operation and in postoperative period in both groups. CONCLUSIONS: The intensity of inflammatory response in CPB patients which is enhanced by massive contact activation of blood and extensive ischemia-reperfusion injury is regulated by the production of antiiflammatory IL- 10 cytokine.

[Transcription factor KLF2 (Krüppel-like factor 2) and natural defence of vascular endothelium]. / Transkripcní faktor KLF2 (Krüppel-like factor 2) a prirozená ochrana cévního endotelu.

Vascular endothelium, monocytes and T-lymphocytes belong to the key cellular populations, which take an active part in the host's defence reactions. A successful course of these reactions is determined by a meticulous control of all phases since the very first steps until final healing of all incurred wounds. Any failure of the control mechanisms may lead to the development of chronic inflammatory diseases with an autoimmune component, such as the rheumatoid arthritis or atherosclerosis. An inflammatory reaction which is already under way is regulated by anti-inflammatory cytokines. However, of equal importance is the maintenance of cellular participants of inflammatory reactions in a quiescent state while no pro-inflammatory stimuli are present. One of the most important endogenous mediators, which prevent a self-initiated activation of endothelial cells, monocytes and T-lymphocytes, is represented by the transcription factor Krüppel-like factor 2. Its impact on the mentioned cells is almost identical with the so-called pleiotropic effects of inhibitors of the enzyme HMG CoA reductase or statins. This review article offers an insight into basic preventive mechanisms exerted by KLF2, notably those related to atherosclerosis.

[Innate immunity, receptors for exogenous and endogenous danger patterns in immunopathogenesis of atherosclerosis--part II: TLR receptors, significance of genetic polymorphism of danger signals receptors]. / Pirrozená imunita, receptory pro exogenní a endogenní nebezpecné vzory v imunopatogenezi aterosklerózy II. cast. Receptory TLR, význam polymorfizmu receptoru pro nebezpecné vzory.

The most important set of receptors for danger patterns are TLR receptors. Together ten different TLR receptors were identified so far. Majority of TLR receptors is expressed on the cell surface to identify extracellulary localized danger signals. Some TLR receptors are also expressed in the intracellular compartment to identify intracellular danger signals. Receptors for danger signals display individual differences delineated by genetic polymorphism. The individual immune reactivity is developed in the context of genetic predisposition and the exposition to variable environmental factors. The differences in an individual immune reactivity are probably responsible for individual susceptibility or resistance to the development of immunopathological reactivity, which is involved in the immunopathogenesis of atherosclerosis.

[Innate immunity, receptors for exogenous and endogenous danger patterns in immunopathogenesis of atherosclerosis--part 1: identification of danger signals by innate immunity]. / Prirozená imunita, receptory pro exogenní a endogenní nebezpecné vzory v imunopatogenezi aterosklerózy I. cást: Prirozená imunita, rozlisení signálu nebezpecí.

Cellular and humoral components of innate immunity are able to identify danger signals both of the exogenous and endogenous origin. Exogenous danger signals are evolutionary conserved mosaics of danger patterns which are frequent in pathogenic microbes. Endogenous danger signals are raised during damage of self structures, by oxidative stress and/or by chemical modification of self molecules. Danger signals are identified by several families of molecules which are expressed on the surfaces of innate immunity cells. Among them the TLR receptors family which is associated with intracellular signaling pathway NF-kappaB is one of the most important. The inflammatory response is induced via activated NF-kappaB transcription factor.