Search results

1

The emerging distinct role of TNF-receptor 2 (p80) signaling in chronic inflammatory disorders

100%

Holtmann M. H., Schuchmann M., Zeller G., Galle P. R., Neurath M. F.

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issue 4

279-287

EN

Tumor necrosis factor (TNF)-alpha is a pleiotropic cytokine with strong proinflammatory and immunomodulatory properties. TNF-alpha plays a critical role in many acute or chronic inflammatory diseases and anti-TNF strategies have proven to be clinically effective. Two TNF-specific cell surface receptors, TNF-R1 (p60) and TNF-R2 (p80), have been identified and the function of these receptors and the downstream intracellular signal-transduction pathways have been extensively studied in vitro. For a long time p60 was considered to be the predominant mediator of TNF signaling, whereas p80 was ascribed only an euxilliary function. However, there is increasing clinica and experimental evidence for an important independent role of p80 signaling in chronic inflammatory conditions. The date, most data exist for Crohn's disease. Upregulation of p80 and increased p80 signaling aggrevates experimental colitis and is likely to contribute to the chronicity of inflammation in vivo. Further studies are required to elucidate critically important steps in TNF signaling that might be dysregulated. This will lead to a better understanding of the pathogenesis of these diseases and poteintially reveal new, more specific therapeutic targets

2

Protein serine/threonine kinases (PKA, PKC and CaMKII) involved in ischemic brain pathology

100%

Domanska-Janik K.

Acta Neurobiologiae Experimentalis

|

1996

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vol. 56

|

issue 2

579-585

EN

The protein serina/threonine kinases which are highly expressed in the central nervous system (CNS) are severely affected by brain ischemia.Irrespective of substantial differences among the particular members of this group of kinases, their responses to ischemic stress show a lot of similarities.Initially they are switched on fy faciliated interaction with their specific activators/second messengers like cyclic AMP, 1,2 -sn-diacylglicrol and particularly Ca2+, then they are translocated to highly specific regions of plasma membranes.After phosphorylation of target proteins, the kinases are deactivated by means access to cAMP. In the case of CaMKII, it is probably achieved by its extensive, inhibitory autophosphorylations, while PKC seems to be proteolytically degraded.These biphasic changes in serine/threonine kinases activity may play a critical role in the evolution of postichemic brain injury and provide a mechanism for a variety of short- and long-term signalling events.

3

Negative signals from FceRI engagement attenuate mast-cell functions

100%

Molfetta R., Peruzzi G., Santoni A., Paolini R.

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2007

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vol. 55

|

issue 4

219-229

EN

Mast cells have long been recognized as the critical tissue-based effector cells in IgE-mediated allergic diseases. Ligation of the high-affinity receptor for IgE (FceRI), constitutively expressed on mast cells, promotes cell activation and immediate release and production of pro-inflammatory mediators. Besides these positive signals, FceRI aggregation has recently been understood to generate negative intracellular signals capable of limiting mast-cell functional responses. This review is aimed at providing a summary of the mechanisms through which FceRI engagement can generate negative signals and regulate mast-cell function. Similar mechanisms are employed by other receptors expressed by immune cells, such as T cell and B cell receptors, pointing to a general concept in negative immunoreceptor signaling.

4

Ethylene and plant defense response

80%

Handschuh L.

Biotechnologia

|

1999

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issue 3

86-93

EN

The simplest plant growth and development hormone, ethylene, belongs (together with S.A. and JA) to key molecules governing the plant defense response. Production of ethylene is stimulated by wounding, flooding, metal ions, senescense and abscission processes, pathogene attack and ethylene itself. High level of ethylene induces the expression of many classes of pathogenesis-related proteins (PR). In order to properly function, ethylene must be precisely regulated, especially at the biosynthesis and signalling pathways. Two main enzymes involved in ethylene biosynthesis are ACC synthase and ACC oxidase. The ethylene signal transduction pathway is very complicated and needs to be further investigated. Ethylene binds to its receptors ETRs, then the signal is transduced to CTR1 and through phosforylating kinases cascades to EINs and EREBPs, directly binding to DNA GCC boxes. As a consequence, many PR proteins are activated.

5

The role of PTEN in allergic inflammation

80%

Lee Y. C.

Archivum Immunologiae et Therapiae Experimentalis

|

2004

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vol. 52

|

issue 4

250-254

EN

Bronchial asthma is a chronic inflammatory disease of the airways, characterized by airway eosinophilia, goblet cell hyperplasia with mucus hyper-secretion, and hyper-responsiveness to inhaled allergens and to non-specific stimuli. Eosinophil accumulation and subsequent activation in bronchial tissues play critical roles in the pathophysiology of bronchial asthma. Many inflammatory mediators attract and activate eosinophils via signal transduction pathways involving an enzyme phosphatidylinositol 3-kinase (PI3- kinase). Studies using wortmannin, a specific inhibitor of PI3-kinase, have revealed the involvement of PI3-kinase in the biochemical transduction of activation signals generated by many inflammatory mediators in eosinophils. Wortmannin prevents the development of airway inflammation, either by inhibiting the eosinophil infiltration of bronchial tissues or their activation on arrival. Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is part of a complex signaling system that affects a variety of important cell functions. PTEN opposes the action of PI3-kinase by dephosphorylating the signaling lipid phosphatidylinositol 3,4,5-triphosphate. Recently we have demonstrated that PTEN expression is diminished in airway epithelial cells of antigen-sensitized and -challenged mice. Administration of PI3-kinase inhibitors or adenoviruses carrying PTEN complementary DNA remarkably reduces eosinophil levels and inflammation. One likely mechanism for this reduction is PTEN-mediated eosinophil degranulation and suppression of interleukin (IL)-4 and IL-5. These findings indicate that use of PTEN may be a good therapeutic strategy for the management of allergic inflammation.

6

cGMP-dependent protein kinases

80%

Kurowska E., Siednienko J., Gorczyca W. A.

Postępy Higieny i Medycyny Doświadczalnej

|

2003

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vol. 57

|

issue 6

631-648

EN

Cyclic GMP is common second messenger in a plethora of processes. Its major intracellular receptors are the cGMP-dependent protein kinases (PKGs). In this minireview we summarise the main results of studies on structure and physiological role of PKGs.

7

Molecular mechanisms of CD40 signaling

80%

Bishop G. A., Hostager B. S.

Archivum Immunologiae et Therapiae Experimentalis

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2001

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vol. 49

|

issue 2

129-138

EN

CD40, a member of the growing tumor necrosis factor receptor (TNF-R) family of molecules, functions as a transmembrane signal receptor in both hematopoietic and non-hematopoietic cell types, although its physiological roles are less well understood in the latter. Much has been learned over the past decade about the role of CD40 signaling in various cellular functions. In addition, some of the molecular events which occur subsequent to CD40 engagement have been characterized, although much remains to be understood. This review will summarize the known important biological roles of CD40, and discuss what is currently known about how CD40 signals.

8

Fc? receptors - properties, binding of IgG and the role in induction of various biological functions in cells

80%

Sokal I.

Postępy Higieny i Medycyny Doświadczalnej

|

1995

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vol. 49

|

issue 1

47-51

9

Multi-functional roles of stat3 revealed by conditional gene targeting

80%

Takeda K., Akira S.

Archivum Immunologiae et Therapiae Experimentalis

|

2001

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vol. 49

|

issue 4

279-284

EN

Signal transducer and activator of transcription (STAT) is a family of transcription factors composed of seven members. Gene-targeted mice of each STAT family protein displayed defective responses to cytokines, demonstrating an important role in cytokine-mediated biological responses. However, unlike the mice lacking other STAT proteins, Stat3-deficient mice died during their early embryogenesis. Therefore, in an attempt to avoid the lethality and assess the role of Stat3 in cytokine-mediated functions in mouse adult tissues, conditional gene targeting utilizing a Cre-loxP system was achieved. By this method, Stat3 was disrupted in several types of tissue, including T cells, macrophages, skin, and mammary gland. Analyses of these Stat3-mutant mice revealed important roles of Stat3 in biological functions in each tissue.

10

Positive and negative regulatory mechanisms in high-affinity IgE receptor-mediated mast cell activation

80%

Roth K., Chen W.-M., Lin T.-J.

Archivum Immunologiae et Therapiae Experimentalis

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2008

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vol. 56

|

issue 6

385-399

EN

Mast cells are important effector cells in allergic inflammatory reactions. The aggregation of the high-affinity IgE receptor (Fc epsilon RI) on the surface of mast cells initiates a complex cascade of signaling events that ultimately leads to the release of various mediators involved in allergic inflammation and anaphylactic reactions. The release of these mediators is tightly controlled by signaling pathways that are propagated through the cell by specific phosphorylation and dephosphorylation events. These events are controlled by protein kinases and protein phosphatases which either positively or negatively regulate the propagation of the signal through the cell. This review summarizes the role of both positive and negative regulators of Fc?RI-induced mast cell activation.

11

The murine Ly49 family: form and function

80%

Makrigiannis A. P., Anderson S. K.

Archivum Immunologiae et Therapiae Experimentalis

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2001

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vol. 49

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issue 1

47-50

EN

The activity of natural killer (NK) cells is regulated by surface receptors that recognize class I MHC. Murine NK cells express a large family of lectin-related receptors (Ly49s) to perform this function, while human NK cells utilize a separate group of proteins containing Ig-related domains (KIRs). Although these receptor families not structurally related, the Ly49 family appears to be the functional equivalent of human KIRs, since it uses similar signal transduction pathways for either activation or inhibition of NK cell function. Therefore, lessons learned from the study of the murine MHC class I receptor system may be relevant to human NK function. This review summarizes the current state of knowledge of the Ly49 family.

12

The role of antisense oligodeoxynucleotides in the investigationa of the molecular phenomenas activated by oncogenes: therapeutical implications

80%

Skorski T., Nieborowska-Skorska M.

Biotechnologia

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1995

|

issue 1

44-55

EN

Antisense oligodeoxynucleotides are well known as specific inhibitor of targeted genes expression. In this paper we demonmstrate that antisenses could be applied for investigation of the molecular mechanisms activated by oncogenes These studies may identify new targets for antisense treatments of tumors.

13

Crosstalk between G protein-coupled receptors and tyrosine kinase signaling: Src take centre stage

80%

Ptasznik A., Gewirtz A. M.

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vol. 48

|

issue 1

27-30

EN

Although the role of G protein-coupled receptors in the regulation of metabolic, secretory and contractile responses is well established, they have only recently been recognized as important mediators of cellular growth and differentiation. G protein-coupled signaling pathways had been previously thought to be totally independent of the tyrosine kinase receptor pathway. It was previously believed that molecular switches responsible for growth factor tyrosine kinase receptor signaling and G protein-coupled signaling were divided into a distinct sets of protein families. Recent evidence has demonstrated, however, that G protein-coupled receptors can crosstalk to tyrosine kinase signaling. In the past few years several groups have found that G protein-coupled receptors utilize non-receptor tyrosine kinases, mostly that of Src family, and some adapter proteins, to regulate tyrosine kinase cascades in cells.

14

Phosphodiesterases of cyclic GMP

80%

Wroblewska H., Gorczyca G. W. A., Gorczyca W. A.

Postępy Higieny i Medycyny Doświadczalnej

|

2001

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vol. 55

|

issue 5

615-627

EN

Phosphodiesterases of cyclic nucleotides (PDEs) are enzymes hydrolyzing cGMP, cAMP or both and are regulated in several different ways. In this paper we summarize current data on structure, cellular and tissue localization, regulation and function of different PDE families that hydrolyze cGMP.

15

The role of TGF-beta signaling in the pathogenesis of fibrosis in scleroderma

80%

Ihn H.

Archivum Immunologiae et Therapiae Experimentalis

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2002

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vol. 50

|

issue 5

325-332

EN

Excessive extracellular matrix (ECM) deposition in the skin, lung, and other organs is a hallmark of systemic sclerosis (SSc). The pathogenesis of SSc is still poorly understood, but increasing evidence suggests that transforming growth factor (TGF)-beta is a key mediator of tissue fibrosis as a consequence of ECM accumulation in pathologic states such as systemic sclerosis. TGF-beta regulates diverse biological activities including cell growth, cell death or apoptosis, cell differentiation, and extracellular matrix (ECM) synthesis. TGF-beta is known to induce the expression of ECM proteins in mesenchymal cells, and to stimulate the production of protease inhibitors that prevent enzymatic breakdown of the ECM. This review focuses on the possible role of TGF-beta in the pathogenesis of fibrosis in SSc.

16

Signaling pathways mediating anti-apoptotic action of neurotrophins

71%

Hetman M., Xia X. Z., Xia Z.

Acta Neurobiologiae Experimentalis

|

2000

|

vol. 60

|

issue 4

531-545

EN

Neurotrophins promote survival and suppress apoptosis in many populations of neurons. Currently, phosphatidylinositol-3 kinase (PI-3K) is recognized as the main mediator of this protective effect. However, most of the data collected so far on the anti-apoptotic signaling of neurotrophins were obtained using trophic withdrawal paradigms. Recent data from our and other groups indicate that extracellular-signal-regulated kinase 1/2 (Erk1/2) may play a critical role in suppressing neuronal apoptosis triggered by cellular damage. Thus, it appears that either Erk1/2 or PI-3K, depending on the nature of the death-inducing stimulus, can mediate anti-apoptotic signaling of neurotrophins. In this review, we discuss the contribution of Erk1/2 and PI-3K to neuroprotection by neurotrophins. We also present data suggesting possible mechanisms by which these pathways might suppress neuronal death.

17

Proteomics of experimental stroke in mice

71%

Focking M., Besselmann M., Trapp T.

Acta Neurobiologiae Experimentalis

|

2006

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vol. 66

|

issue 4

273-278

EN

Multi-Western blots of more than 400 proteins were performed from brain extracts of mice submitted to transient focal ischemia induced by 1 h middle cerebral artery (MCA) thread occlusion. Measurements were carried out in groups of six animals in sham-operated controls, at the end of 1 h ischemia, and after 3 and 12 h recirculation. After MCA occlusion up to 45% of proteins were up- or downregulated in the ipsilateral hemisphere by a factor of 1.5 or more, as compared to sham-operated controls. The temporal regulation of several proteins in the ischemia-affected hemisphere after 1 h MCA thread occlusion is described. In the non-ischemic hemisphere the number of regulated proteins was close to 50%, indicating a hitherto unrecognized involvement of the opposite side. The proteomic approach of brain injury analysis goes beyond previous screenings of gene expression at the transcriptional level and although our study provides further evidence for the complexity of multiinjury pathways in the evolution of ischemic brain damage it may help to identify key mediators of ischemic injury.

18

Molecular aspects in the pathogenesis of human systemic lupus erythematosus

71%

Liossis S.-N. C., Tsokos G. C.

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vol. 48

|

issue 1

11-19

EN

Systemic lupus erythematosus is a common and often devastating systemic autoimmune disease of unknown etiology. In this communication we review the latest developments of the molecular pathogenesis of human lupus. Novel genetic studies of multiplex lupus families have revealed potential disease-associated genome intervals, put special emphasis on genetic loci mapping in the long arm of chromosome 1 and have underscored the complexity of the underlying genetic background. New data have emerged on the role of estrogens in the function of lymphocytes and a number of studies have recently emphasized the relative Th-1/Th-2 cytokine imbalance in favor of a Th-2 type cytokine immune response. Finally, novel experiments have revealed an abnormal antigen receptor- -mediated signaling process in lupus T and B cells, which may influence the aberrant expression and function of costimulatory molecules as well as of other aspects of immune cell function. It is important to decipher the underlying molecular mechanisms that govern the expression of human lupus, because we may design novel, rational approaches in the treatment of a human lupus, a disease that has high morbidity and mortality.

19

A role of protein kinase C isoforms in tumorigenicity and apoptotic cells death

71%

Rybczynska M., Ksiazek K., Kaczmarek J.

Postępy Higieny i Medycyny Doświadczalnej

|

2000

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vol. 54

|

issue 6

777-796

EN

Protein kinase C comprises a family of at least 13 distinct serine/threonine kinase isoenzymes that have important action in transmembrane signal transduction pathways and have been reported to regulate cell proliferation, differentiation, cell-to-cell interaction, cytoskeletal functions, gene transcription, apoptosis and drug resistance. The results of investigations show differential redistribution isozymes in each organs and their specyfic activity in determined diseases.

20

The cGMP synthesis and PKG1 expression in murine lymphoid organs

71%

Kurowska E., Kobialka M., Ziolo E., Strzadala L., Gorczyca W. A.

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issue 4

289-295

EN

Numerous reports indicate that cyclic 3',5' guanosine monophosphate (cGMP) is involved in the regulation of immune processes. However, the mechanisms responsible for the synthesis of this nucleotide and its signaling pathways in immune cells are still not well recognized. The aim of our study was to establish: 1) which form of guanylyl cyclase synthesizes cGMP in murine lymphoid organs and 2) whether the same organs express the isoforms PKG1alpha and/or PKG1beta of protein kinase G, known as a possible target for synthesized cGMP. Cells isolated from thymus, lymph nodes, and spleen were treated with activators (SNP, ANP, CNP, STa) of soluble or particulate cyclases. Sodium nitroprusside (SNP) elevated intracellular cGMP 2-fold in thymic and lymph node cells and about 10-fold in spleen cells. Atrial natriuretic peptide (ANP) caused modest but statistically significant increases of cGMP in cells of all the organs. Additionally, spleen cells elevated their cGMP content about 2-fold in response to C-type natriuretic protein (CNP). In cellular homogenates of all the analyzed organs, the antibody anti-PKG1beta stained the 78 kDa band corresponding to the molecular mass of PKG1. Only homogenates of spleen cells were stained by the antibody recognizing PKG1alpha. Our results indicate that in all the investigated organs, cGMP may be synthesized mainly by soluble guanylyl cyclases in response to nitric oxide. The modest increase of cGMP upon stimulation by ANP suggests that in all these organs either exist only a small subpopulation of cells that express particulate cyclase GC-A or GC-A is expressed at very low level. In spleen cells, however, cyclase GC-B appears to be the more active enzyme. Elevated cGMP concentration may in turn activate PKG1beta in thymus, lymph node, and spleen cells and also PKG1alpha in spleen cells.

Refine search results

The emerging distinct role of TNF-receptor 2 (p80) signaling in chronic inflammatory disorders

Protein serine/threonine kinases (PKA, PKC and CaMKII) involved in ischemic brain pathology

Negative signals from FceRI engagement attenuate mast-cell functions

Ethylene and plant defense response

The role of PTEN in allergic inflammation

cGMP-dependent protein kinases

Molecular mechanisms of CD40 signaling

Fc? receptors - properties, binding of IgG and the role in induction of various biological functions in cells

Multi-functional roles of stat3 revealed by conditional gene targeting

Positive and negative regulatory mechanisms in high-affinity IgE receptor-mediated mast cell activation

The murine Ly49 family: form and function

The role of antisense oligodeoxynucleotides in the investigationa of the molecular phenomenas activated by oncogenes: therapeutical implications

Crosstalk between G protein-coupled receptors and tyrosine kinase signaling: Src take centre stage

Phosphodiesterases of cyclic GMP

The role of TGF-beta signaling in the pathogenesis of fibrosis in scleroderma

Signaling pathways mediating anti-apoptotic action of neurotrophins

Proteomics of experimental stroke in mice

Molecular aspects in the pathogenesis of human systemic lupus erythematosus

A role of protein kinase C isoforms in tumorigenicity and apoptotic cells death

The cGMP synthesis and PKG1 expression in murine lymphoid organs