Home About us Contact
|
Home About us Contact | ||
|
|
||
Chemokine Interleukin (chemokine + interleukin)
Selected AbstractsOsteoblast-Derived TGF-,1 Stimulates IL-8 Release Through AP-1 and NF-,B in Human Cancer Cells,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2008Yi-Chin Fong Abstract Introduction: The bone marrow microenvironment is further enriched by growth factors released during osteoclastic bone resorption. It has been reported that the chemokine interleukin (IL)-8 is a potent and direct activator of osteoclastic differentiation and bone resorption. However, the effect of bone-derived growth factors on the IL-8 production in human cancer cells and the promotion of osteoclastogenesis are largely unknown. The aim of this study was to investigate whether osteoblast-derived TGF-,1 is associated with osteolytic bone diseases. Materials and Methods: IL-8 mRNA levels were measured using RT-PCR analysis. MAPK phosphorylation was examined using the Western blot method. siRNA was used to inhibit the expression of TGF-,1, BMP-2, and IGF-1. DNA affinity protein-binding assay and chromatin immunoprecipitation assays were used to study in vitro and in vivo binding of c- fos, c- jun, p65, and p50 to the IL-8 promoter. A transient transfection protocol was used to examine IL-8, NF-,B, and activator protein (AP)-1 activity. Results: Osteoblast conditioned medium (OBCM) induced activation of IL-8, AP-1, and NF-,B promoter in human cancer cells. Osteoblasts were transfected with TGF-,1, BMP-2, or IGF-1 small interfering RNA, and the medium was collected after 48 h. TGF-,1 but not BMP-2 or IGF-1 siRNA inhibited OBCM-induced IL-8 release in human cancer cells. In addition, TGF-,1 also directly induced IL-8 release in human cancer cells. Activation of AP-1 and NF-,B DNA-protein binding and MAPKs after TGF-,1 treatment was shown, and TGF-,1,induced IL-8 promoter activity was inhibited by the specific inhibitors of MAPK cascades. Conclusions: In this study, we provide evidence to show that the osteoblasts release growth factors, including TGF-,1, BMP-2, and IGF-1. TGF-,1 is the major contributor to the activation of extracellular signal-related kinase (ERK), p38, and c-Jun N-terminal kinase (JNK), leading to the activation of AP-1 and NF-,B on the IL-8 promoter and initiation of IL-8 mRNA and protein release, thereby promoting osteoclastogenesis. [source] Activation of NF-,B and IL-8 by Yersinia enterocolitica invasin protein is conferred by engagement of Rac1 and MAP kinase cascadesCELLULAR MICROBIOLOGY, Issue 12 2003Guntram A. Grassl Summary Yersinia enterocolitica triggers activation of the nuclear factor (NF)-,B and production of the proinflammatory chemokine interleukin (IL)-8 in intestinal epithelial cells. This activation is due to adhesion of the bacteria via their outer membrane protein invasin to the host cells. Using Clostridium difficile toxins that specifically inactivate small GTPases, and transfection of inhibitory proteins of the Rho-GTPases, we demonstrate that Rac1, but not Cdc42 or Rho, is required for activation of NF-,B by invasin. Invasin activated the mitogen activated protein kinases (MAPK) p38 and c-Jun N-terminal protein kinase (JNK) but not extracellular signal regulated kinase (ERK). The functional relevance of these pathways for invasin-mediated IL-8 expression was assessed by protein kinase inhibitors and dominant-negative kinase mutants. While NF-,B and JNK contribute to IL-8 transcription, p38 MAPK also acts through stabilization of IL-8 mRNA, as confirmed by quantitative RT-PCR and electrophoretic mobility shift assays. Transfection experiments with I-,B kinase (IKK)1 and IKK2 mutants indicate that the release of NF-,B from its cytoplasmic inhibitor I-,B and its translocation into the nucleus is mediated by these kinases. Our data identify Rac1 as a key intermediate in invasin-triggered IL-8 synthesis and demonstrate that maximum IL-8 induction involves several MAP kinase cascades. [source] Anti-inflammatory properties of heat shock protein 70 and butyrate on Salmonella -induced interleukin-8 secretion in enterocyte-like Caco-2 cellsCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 1 2005J. J. Malago Summary Intestinal epithelial cells secrete the chemokine interleukin (IL)-8 in the course of inflammation. Because heat shock proteins (Hsps) and butyrate confer protection to enterocytes, we investigated whether they modulate Salmonella enterica serovar Enteritidis (S. serovar Enteritidis)-induced secretion of IL-8 in enterocyte-like Caco-2 cells. Caco-2 cells incubated with or without butyrate (0,20 m M, 48 h) were infected with S. serovar Enteritidis after (1 h at 42°C, 6 h at 37°C) or without prior heat shock (37°C). Levels of Hsp70 production and IL-8 secretion were analysed using immunostaining of Western blots and enzyme-linked immunosorbent assay (ELISA), respectively. The cells secreted IL-8 in response to S. serovar Enteritidis and produced Hsp70 after heat shock or incubation with butyrate. The IL-8 secretion was inhibited by heat shock and butyrate concentrations as low as 0·2 m M for crypt-like and 1 m M for villous-like cells. In a dose-dependent manner, higher butyrate concentrations enhanced IL-8 secretion to maximal levels followed by a gradual but stable decline. This decline was associated with increasing production of Hsp70 and was more vivid in crypt-like cells. In addition, the higher concentrations abolished the heat shock inhibitory effect. Instead, they promoted the IL-8 production in heat-shocked cells even in the absence of S. serovar Enteritidis. We conclude that heat shock and low concentrations of butyrate inhibit IL-8 production by Caco-2 cells exposed to S. serovar Enteritidis. Higher butyrate concentrations stimulate the chemokine production and override the inhibitory effect of the heat shock. The IL-8 down-regulation could in part be mediated via production of Hsp70. [source] Long-term effect of full-mouth tooth extraction on the responsiveness of peripheral blood monocytesJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 8 2003Schelte J. Fokkema Abstract Background: As some residual inflammation may remain after periodontal therapy, the present pilot study investigated the long-term effect of full-mouth tooth extraction therapy on the responsiveness of peripheral blood monocytes in a case with generalized terminal adult periodontitis. Methods: Before and 3, 9, 20 and 32 months after therapy, venous blood was collected. Total and differential white blood cell counts were determined and whole blood cell cultures (WBCC) were incubated with lipopolysaccharide (LPS) to stimulate the production of inflammatory mediators by monocytes. Results: After full-mouth tooth extraction, the numbers of total peripheral white blood cells and neutrophils decreased over time. The release of the chemokines interleukin (IL)-8 and macrophage chemoattractant protein (MCP)-1 in the cultures decreased twofold over time, whereas no changes were seen for the other studied cytokines, chemokines and prostaglandin E2. Conclusion: On the basis of previous studies and the present case, the high production of IL-8 and MCP-1 by monocytes in LPS-stimulated WBCC from periodontitis patients is most likely acquired, as their levels decrease over time when the periodontal infection is controlled. The possible connection between periodontitis and atherosclerosis through IL-8 and MCP-1 is discussed. Zusammenfassung Hintergrund: Da nach der parodontalen Therapie eine restliche Entzündung zurückbleiben kann, untersucht die vorliegende Studie den Langzeiteffekt einer vollständigen Zahnextraktion auf die Ansprechbarkeit der peripheren Blutmonozyten in einem Fall mit generalisierter unheilbarer Erwachsenen-Parodontitis. Methoden: Vor und 3, 9, 20 und 32 Monaten nach der Therapie wurde venöses Blut gesammelt. Der totale und differenzierte weiße Blutzellgehalt wurden bestimmt, und eine gesamte Blutzellkultur (WBCC) wurde mit Lipopolysaccharid inkubiert, um die Produktion von Entzündungsmediatoren durch Lymphozyten zu stimulieren. Ergebnisse: Nach der vollständigen Zahnextraktion verringerte sich die Zahl der totalen peripheren weißen Blutzellen und der Neutrophilen über die Zeit. Die Freisetzung des Chemokins Interleukin 8 (IL-8) und des Makrophagen chemoattraktanten Proteins (MCP) ,1 in den Kulturen verringerte sich zweifach über die Zeit, während für die anderen beobachteten Cytokine, Chemokine und Prostaglandin E2 keine Veränderungen festgestellt wurden. Schlussfolgerung: Auf der Basis vorheriger Studien und des vorliegenden Falls ist die hohe Produktion von IL-8 und MCP-1 durch Monozyten in LPS stimulierten WBCC von Parodontitis-Patienten sehr wahrscheinlich anzunehmen, da ihr Level über die Zeit abnimmt, wenn die parodontale Infektion kontrolliert ist. Die mögliche Verbindung zwischen Parodontitis und Arteriosklerose durch IL-8 und MCP-1 wird diskutiert. Résumé Contexte: Puisqu'après traitement parodontal, une inflammation résiduelle peut subsister, cette étude se propose de rechercher les effets à long terme de l'extraction complète des dents sur la réponse des monocytes périphériques dans un cas de parodontite de l'adulte terminale généralisée. Méthodes: Des prélèvements sanguins veineux ont été réalisés avant et 3, 9, 20 et 32 mois après traitement. Les comptages totaux et relatifs des cellules blanches sanguines furent déterminés et les cultures complètes de cellules sanguines (WBCC) furent incubées avec du lipopolysaccharide pour stimuler la production des médiateurs de l'inflammation par les monocytes. Résultats: Après l'extraction complète des dents, les nombres de cellules sanguines blanches totales périphériques et des neutrophiles diminuaient au cours du temps. Le relargage des chimiokines interleukine (IL)-8 et protéine chimio-attractante du macrophage (MCP)-1 dans les cultures diminuait deux fois au cours du temps, alors qu'aucun changement n'était observé pour les autres cytokines étudiées, chimiokines et prostaglandine E2. Conclusion: Sur la base d'études préalables, et les résultats issus de ce cas présent, la forte production d'IL-8 et de MCP-1 par les monocytes dans les WBCC stimulés par le LPS chez des patients atteints de parodontite semble être vraisemblablement acquise puisque leurs niveaux diminuent lorsque l'infection parodontale est contrôlée. La relation possible entre parodontite et l'athérosclérose par IL-8 et MCP-1 est discutée. [source] | ||||||||||