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Biomedical subjects

K Riehemann

Publications and source records attributed to K Riehemann.

10 recordsLinked to original sources

A novel ligand of the formyl peptide receptor: annexin I regulates neutrophil extravasation by interacting with the FPR.

The glucocorticoid-regulated protein annexin I (lipocortin I) has been shown to mediate antiinflammatory activities of glucocorticoids, but the molecular basis of its action has remained elusive. Here we show that annexin I acts through the formyl peptide receptor (FPR) on human neutrophils. Peptides derived from the unique N-terminal domain of annexin I serve as FPR ligands and trigger different signaling pathways in a dose-dependent manner. Lower peptide concentrations possibly found in inflammatory situations elicit Ca2+ transients without fully activating the MAP kinase pathway. This causes a specific inhibition of the transendothelial migration of neutrophils and a desensitization of neutrophils toward a chemoattractant challenge. These findings identify annexin I peptides as novel, endogenous FPR ligands and establish a mechanistic basis of annexin I-mediated antiinflammatory effects.

Amino Acid Sequence↗

Plant extracts from stinging nettle (Urtica dioica), an antirheumatic remedy, inhibit the proinflammatory transcription factor NF-kappaB.

Activation of transcription factor NF-kappaB is elevated in several chronic inflammatory diseases and is responsible for the enhanced expression of many proinflammatory gene products. Extracts from leaves of stinging nettle (Urtica dioica) are used as antiinflammatory remedies in rheumatoid arthritis. Standardized preparations of these extracts (IDS23) suppress cytokine production, but their mode of action remains unclear. Here we demonstrate that treatment of different cells with IDS23 potently inhibits NF-kappaB activation. An inhibitory effect was observed in response to several stimuli, suggesting that IDS23 suppressed a common NF-kappaB pathway. Inhibition of NF-kappaB activation by IDS23 was not mediated by a direct modification of DNA binding, but rather by preventing degradation of its inhibitory subunit IkappaB-alpha. Our results suggests that part of the antiinflammatory effect of Urtica extract may be ascribed to its inhibitory effect on NF-kappaB activation.

Animals↗

Differential expression of annexins I, II and IV in human tissues: an immunohistochemical study.

Annexins constitute a family of Ca2+- and phospholipid-binding proteins. Although their functions are still not clearly defined, several members of the annexin family have been implicated in membrane-related events along exocytotic and endocytotic pathways. To elucidate a possible correlation of those functional proposals with the tissue distribution of annexins, we analysed immunohistochemically the expression of annexins I, II and IV in a broad variety of human tissues. Annexins I and II were chosen for this study since their functionally relevant N-terminal domains are structurally closely related, whilst annexin IV is structurally less related to the former two proteins. The study revealed distinct expression patterns of annexins I, II and IV throughout the body. Annexin I was found in leucocytes of peripheral blood, tissue macrophages and T-lymphocytes and in certain epithelial cells (respiratory and urinary system, superficial cells of non-keratinised squamous epithelium), annexin II in endothelial cells, myoepithelial cells and certain epithelial cells (mainly respiratory and urinary system), whereas annexin IV was almost exclusively found in epithelial cells. Epithelia of the upper respiratory system, Bowman's capsule, urothelial cells, mesothelial cells, peripheral nerves, the choroid plexus, ependymal cells and pia mater and arachnoid of meninges generally strongly expressed all three annexins investigated. The characteristic expression in different tissues and the intracellular distribution indicates that the three annexins investigated are involved in aspects of differentiation and/or physiological functions specific to these tissues.

Annexin A1↗

Regulation of NF-kappa B activation by MAP kinase cascades.

Transcription factor NF-kappa B plays a crucial role in the regulation of numerous genes involved in the inflammatory response and control of cell death. Activation of NF-kappa B is mediated through the phosphorylation of its inhibitory subunit I kappa B, followed by the subsequent degradation of I kappa B at the proteasome. A second level of control involves phosphorylation events of NF-kappa B in the cell nucleus. The kinases that regulate these processes are rather undefined. NF-kappa B activation is induced by a great variety of predominantly pathogenic and noxious stimuli. A similar spectrum of conditions triggers the activation of two mitogen-activated protein (MAP) kinase cascades, designated as the JNK and p38 kinase pathways. Several points of evidence suggest that MAP kinases can participate in the regulation of NF-kappa B transcriptional activity. Here, we will review very recent data demonstrating that both the JNK and the p38 pathways are involved in the activation of NF-kappa B in the cytoplasm as well as in modulation of its transactivating potential in the nucleus.

Animals↗

Immunohistochemically detectable bcl-2 expression in colorectal carcinoma: correlation with tumour stage and patient survival.

The bcl-2 gene encodes for a mitochondrial membrane proto-oncoprotein, the expression of which is known to suppress programmed cell death (apoptosis). In the present study the prognostic value of bcl-2 proto-oncoprotein was immunohistochemically investigated in a series of 104 colorectal carcinomas. The bcl-2 staining patterns were semiquantitatively assessed and correlated with the pTNM stage, Dukes' classification, lymphocytic infiltration (Jass classification) and tumour grade as well as parameters not associated with prognosis (gender, age, tumour site, histological tumour type). Statistical analysis was carried out using the Kaplan-Meier method, the log-rank test, hazard ratios and their confidence intervals. Fifty-five out of 104 cases completely lacked immunohistochemical bcl-2 expression. Fewer than 5% of bcl-2-positive cells were found in 25, 5-50% in 17 and more than 50% in five cases. The extent of bcl-2 expression by tumour cells decreased significantly with respect to increasing tumour size (P < 0.05), decreasing lymphocytic infiltration (P < 0.05) and chance of poor clinical outcome (P < 0.05), but not with worsening of Dukes stages. In multivariate analysis (Cox regression model) bcl-2 expression remained as an independent prognostic parameter with Dukes' classification as stratification factor (P < 0.001). Although the biological functions of bcl-2 protein are not yet well understood, our results provide further evidence that bcl-2 oncoprotein appears to be associated with favourable clinical outcome. Thus immunohistochemical bcl-2 phenotyping of colorectal carcinoma may contribute in future to the clinical management of these patients.

Adult↗

[A standardized AgNOR stain method for formalin fixed and paraffin embedded material].

Visualization of proteins associated with nucleolar organizer regions proteins (AgNORs) on formalin-fixed and paraffin-embedded archival tissues is substantially improved after application of wet autoclave pretreatment. Silver staining results are comparable to those obtained on tissues processed in alcohol based fixatives, illustrating AgNORs as substructures of the nucleoli without any staining artefacts. A highly reproducible staining quality was achieved irrespective of tissue origin or duration of formalin fixation. As a result of this novel and simple method, the grounds have been prepared for standardized AgNOR quantification on archival material.

Fixatives↗

[Moist autoclaving. A simplified method for antigen unmasking].

Wet autoclaving is a simple, reliable and time-effective method for antigen retrieval in routinely processed archival material. Both routine diagnostic (e.g., oestrogen and progesterone receptors, cytoskeletal proteins) and research antibodies (e.g. various p53 antibodies, mdm-2, bcl-2, MIB-1) are reported to demonstrate its application. We autoclaving may allow successful application of antibodies in paraffin-embedded tissues designed for use on frozen sections. The technique has the potential to reliably handle up to 200 sections at a time, without evidence of any significant damage to the sections or nuclear morphology.

Antigens, Neoplasm↗

Wet autoclave pretreatment improves the visualization of silver-stained nucleolar organizer-region-associated proteins in routinely formalin-fixed and paraffin-embedded tissues.

This study describes the effect of wet autoclave pretreatment of routinely formalin-fixed and paraffin-embedded tissues on silver-stained nucleolar organizer-region-associated proteins (AgNORs) staining. The treatment of sections at superheated steam temperature (120 degrees C) before silver incubation leads to a significantly better discrimination of single-interphase AgNORs. Counting "black dots" both by eye and by means of a computer-aided image-analyzing system revealed considerably higher AgNOR mean numbers per nucleus in all pretreated cases when compared with the respective untreated controls. However, mean AgNOR numbers increased after autoclave pretreatment in a nonlinear manner (pairwise comparison by means of Spearman's Rank correlation coefficient: rho = 0.5), whereas measurement of the AgNOR area was less influenced by autoclave pretreatment (rho = 0.8). It is concluded that wet autoclave pretreatment of routinely formalin-fixed and paraffin-embedded archival material should be applied before AgNOR staining, particularly when quantitation of AgNORs involves counting procedures.

Adenocarcinoma↗