Journal of inflammation最新文献

{"title":"Role of adhesion molecules and platelets in TNF-induced adhesion of tumor cells to endothelial cells: implications for experimental metastasis.","authors":"B Stoelcker,&nbsp;M Hafner,&nbsp;P Orosz,&nbsp;B Nieswandt,&nbsp;D N Männel","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Mechanisms for TNF-enhanced adhesion of tumor cells to endothelial cells were investigated for their in vivo relevance in a model of experimental metastasis. Mouse fibrosarcoma and thymoma cells were used to analyze TNF-modified adherence to three different mouse endothelioma cell lines and the results were compared to the in vivo colonization behavior of the tumor cells. TNF enhanced tumor cell adhesion in vitro and extravasation in vivo with similar characteristics. The role of different adhesion molecules in these experimental systems was tested. Blocking of ICAM-1, LFA-1, VCAM-1, E-selectin, and P-selectin did not reduce TNF-enhanced metastasis even though tumor cell adhesion in vitro was reduced. However, the correlation between inhibition of integrin binding and inhibition of metastasis achieved with competing peptides indicated an important role for extracellular matrix components in tumor cell attachment. Platelets play a dual role: although in vitro platelets prevented tumor cell adhesion to endothelial cells, in vivo platelet-depletion of mice reduced metastasis.</p>","PeriodicalId":79405,"journal":{"name":"Journal of inflammation","volume":"46 3","pages":"155-67"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19813301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetics of tumour necrosis factor-alpha in autoimmune, infectious, and neoplastic diseases.","authors":"A G Wilson,&nbsp;F S di Giovine,&nbsp;G W Duff","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Tumour necrosis factor-alpha (TNF-alpha) is a potent immunomediator and proinflammatory cytokine that has been implicated in the pathogenesis of a large number of human diseases. The location of its gene with the major histocompatibility complex and biological activities have raised the possibility that polymorphism within this locus may contribute to the genetic association of this region of the genome with a wide range of autoimmune and infectious diseases. This review discusses the genetics of the TNF locus in several of the major autoimmune diseases and also in relation to infectious and neoplastic diseases. There is increasing evidence that genetic variation within the TNF locus is important in determining susceptibility to, or severity of, a significant number of these conditions.</p>","PeriodicalId":79405,"journal":{"name":"Journal of inflammation","volume":"45 1","pages":"1-12"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18588214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MIP-1 gamma: molecular cloning, expression, and biological activities of a novel CC chemokine that is constitutively secreted in vivo.","authors":"A N Poltorak,&nbsp;F Bazzoni,&nbsp;I I Smirnova,&nbsp;E Alejos,&nbsp;P Thompson,&nbsp;G Luheshi,&nbsp;N Rothwell,&nbsp;B Beutler","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We have identified a novel CC chemokine family member, herein termed MIP-1 gamma in view of its similarity to existing members of the MIP-1 group. The murine protein has a predicted length of 100 amino acids. Like MIP-1 alpha, recombinant MIP-1 gamma acts as a pyrogen when administered intracerebroventricularly. MIP-1 gamma and MIP-1 alpha engage the same high-affinity receptor on neutrophils, activating calcium release within seconds following cell contact. Pretreatment with either chemokine abolishes responses to the other, and to itself, suggesting utilization of a common signaling pathway. However, unlike MIP-1 alpha or any of the other CC chemokines, MIP-1 gamma is expressed constitutively by a wide variety of tissues, and circulates in the blood of healthy mice at concentrations of approximately 1 microgram/ml (90 nM). It would therefore be predicted that MIP-1 gamma occupies most of the CC chemokine receptors that exist in the intravascular compartment. As such it might, under normal circumstances, markedly influence responses to the inducible CC chemokines.</p>","PeriodicalId":79405,"journal":{"name":"Journal of inflammation","volume":"45 3","pages":"207-19"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19577558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of and sensitization to the lethal effects of tumor necrosis factor.","authors":"P Brouckaert,&nbsp;C Libert,&nbsp;A Cauwels,&nbsp;B Everaerdt,&nbsp;W Van Molle,&nbsp;P Ameloot,&nbsp;Y Gansemans,&nbsp;B Grijalba,&nbsp;N Takahashi,&nbsp;M J Truong,&nbsp;P Van Leuven,&nbsp;W Fiers","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The extension of the positive results obtained with tumor necrosis factor (TNF) in the locoregional treatment of cancer to systemic treatments requires the selective inhibition of its shock-inducing properties. In this paper, recent data regarding the mechanisms by which infections and tumors render mice extremely sensitive to the lethal effects of TNF as well as regarding the inhibition of the dose-limiting toxicities, hypotension and hepatotoxicity, are summarized. An interleukin-12 (IL-12) driven induction of interferon-gamma (IFN-gamma), probably in synergism with endogenous TNF, was found to mediate infection-induced sensitization. The sensitization induced by tumors develops independent of the IL-12/IFN-gamma axis but ultimately leads to a common step, which can be inhibited by alpha-CD11a and is specific for sensitization. Hypotension can be inhibited by methylene blue (MB), an inhibitor of the nitric oxide (NO)-induced activation of the cytosolic guanylate cyclase, without the indispensable protective properties of NO being affected. Finally, two acute phase proteins, alpha 1-acid-glycoprotein (AGP) and alpha 1-antitrypsin (AT), were able to protect against the TNF-induced liver failure. None of these three inhibitors seems to affect the antitumor effects of TNF.</p>","PeriodicalId":79405,"journal":{"name":"Journal of inflammation","volume":"47 1-2","pages":"18-26"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19877891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RAW264 macrophages stably transfected with an HIV-1 LTR reporter gene provide a sensitive bioassay for analysis of signalling pathways in macrophages stimulated with lipopolysaccharide, TNF-alpha or taxol.","authors":"M J Sweet,&nbsp;D A Hume","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Bacterial lipopolysaccharide (LPS) modulates expression of a variety of genes in macrophages, and additionally activates viral promoters including the HIV-1 LTR. The HIV-1 LTR driving the luciferase reporter gene was stably transfected into the murine macrophage cell line, RAW264. In stably transfected cells, luciferase activity was LPS-dependent. As little as 0.01 ng/ml LPS was sufficient to increase luciferase activity over basal levels with maximal stimulation resulting in a 10- to 20-fold response. The cells also responded to human and murine tumour necrosis factor (TNF alpha). Endogenous TNF alpha was not involved in LPS responses, since pretreatment with alpha-TNF alpha antibody did not affect activation. Induction of HIV-1 LTR activity by LPS occurred independently of phorbol myristate acetate (PMA) sensitive protein kinase C (PKC), since depletion of PKC by prolonged exposure to PMA blocked TNF alpha and PMA responses but was not able to abolish LPS action on these cells. Taxol (5-20 micrograms/ml), a chemotherapeutic agent which mimics LPS action on macrophages, was also able to increase expression of the reporter gene driven by the HIV-1 LTR. However, lower doses of taxol that were not sufficient to trans-activate the LTR or to induce TNF alpha expression were cytotoxic to RAW264 cells suggesting that the cytotoxic and LPS-like activities of taxol were not linked. This cell line provides a convenient method for detecting LPS-like activity and is a useful tool for examining LPS and TNF alpha signalling pathways.</p>","PeriodicalId":79405,"journal":{"name":"Journal of inflammation","volume":"45 2","pages":"126-35"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18588801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Malaria-specific metabolite hemozoin mediates the release of several potent endogenous pyrogens (TNF, MIP-1 alpha, and MIP-1 beta) in vitro, and altered thermoregulation in vivo.","authors":"B A Sherry,&nbsp;G Alava,&nbsp;K J Tracey,&nbsp;J Martiney,&nbsp;A Cerami,&nbsp;A F Slater","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>A characteristic feature of malaria infection is the occurrence of periodic bouts of fever. Experimental and clinical studies have strongly implicated inflammatory cytokines, like tumour necrosis factor (TNF), in the induction of these intermittent fevers [Clark et al., Infect Immunol 32:1058-1066, 1981; Clark et al., Am J Pathol 129:192-199, 1987; Karunaweera et al., Proc Natl Acad Sci USA 89:3200-3203, 1992], but the malaria-specific metabolite(s) which induce the production of such endogenous pyrogens have not yet been fully characterized. It is well known that during the course of malaria infection, a unique schizont component, alternatively referred to as \"malaria pigment\" or hemozoin, is released along with merozoites as the host erythrocyte bursts [Urquhart, Clin Infect Dis 19:117-131, 1994]. We have recently determined that the core structure of hemozoin comprises a novel insoluble polymer of heme units linked by iron-carboxylate bonds [Slater et al., Proc Natl Acad Sci USA 88:325-329, 1991; Slater et al., Nature 355:167-169, 1992]. We now report that purified native, as well as chemically synthesized, hemozoin crystals potently induce the release of several pyrogenic cytokines, including TNF, MIP-1 alpha, and MIP-1 beta, from murine macrophages and human peripheral blood monocytes in vitro. Also, intravenous administration of chemically synthesized preparations of hemozoin to anaesthetized rats results in a marked drop in body temperature. A similar drop in body temperature is observed following the intravenous injection of other well-characterized pyrogenic cytokines (e.g., TNF) which are known to induce a fever response in awake animals, and is thought to reflect the inability of rats to appropriately regulate their body temperature while anaesthetized. As a consequence of its ability to induce pyrogenic cytokines in vitro, and thermal dysregulation in vivo, we propose that this unique parasite metabolite is an important pyrogen released by malaria parasites at schizogomy, which acts by eliciting the production of a group of potent endogenous pyrogens, which include MIP-1 alpha and MIP-1 beta, as well as TNF, in macrophages.</p>","PeriodicalId":79405,"journal":{"name":"Journal of inflammation","volume":"45 2","pages":"85-96"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18589354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacterial lipopolysaccharide binds to CD14 in low-density domains of the monocyte-macrophage plasma membrane.","authors":"P Y Wang,&nbsp;R L Kitchens,&nbsp;R S Munford","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We report that gram-negative bacterial lipopolysaccharide (LPS) binds to CD14 on lipid-enriched, low-density domains of the human monocyte-macrophage (THP-1 cell) plasma membrane. After brief incubation with [3H]LPS under conditions that prevent its internalization, THP-1 cells were disrupted using a detergent-free method and plasma membrane fragments were separated on density gradients. The [3H]LPS-binding fragments had low bouyant densities and were enriched, when compared to high-density membrane fragments, in CD14 (a receptor for LPS and other microbial molecules), p53/56lyn, GTP-binding proteins, ouabain-inhibitable Na+/K+ ATPase, sphingomyelin, and GM1 ganglioside. Monoclonal anti-CD14 antibody 60bca blocked [3H]LPS binding to these membrane fragments. Immunoelectron microscopic analysis identified clusters of CD14 on both large (200-1,000 nm) and small (< or = 200 nm) low-density membrane fragments. GM1 and CD14 were usually found on the same fragments, yet their distributions on those fragments infrequently overlapped. These cells seem to lack arrays of caveolae, the ordered membrane structures that harbor glycosylphosphatidyl-anchored proteins and GM1 in many other cell types. Finding that LPS binds to CD14 predominantly in low-density plasma membrane domains suggests, however, that discrete regions of the monocyte-macrophage plasma membrane may be organized to facilitate rapid responses to, and internalization of, molecules that bind CD14.</p>","PeriodicalId":79405,"journal":{"name":"Journal of inflammation","volume":"47 3","pages":"126-37"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20066034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hemorrhage and resuscitation alter the expression of ICAM-1 and P-selectin in mice.","authors":"R Shenkar,&nbsp;A J Cohen,&nbsp;D Vestweber,&nbsp;Y E Miller,&nbsp;R Tuder,&nbsp;E Abraham","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Acute inflammatory lung injury is a common clinical occurrence following blood loss and trauma, and is characterized by massive neutrophil infiltration into the lung. In order to better examine cell trafficking that may contribute to lung injury in this setting, we investigated in vivo mRNA levels and immunohistochemically determined expression of the adhesion molecules P-selectin and the intercellular adhesion molecule (ICAM)-1 in murine lungs over the 3-day period following hemorrhage and resuscitation. Significant increases in P-selectin mRNA levels were present in lungs obtained 3 days after hemorrhage. ICAM-1 mRNA levels were significantly increased 6 and 72 hr after hemorrhage. Immunohistochemical staining for P-selectin was enhanced on pulmonary vascular endothelium in all visible vessels at 6, 24, and 72 hr after hemorrhage. ICAM-1 immunoreactivity was significantly increased on the alveolar epithelium at 6 and 72 hr post-hemorrhage. These results suggest that increased expression of adhesion molecules in the lung at early post-hemorrhage timepoints may contribute to neutrophil infiltration into the lungs and the frequent development of acute lung injury following blood loss and trauma.</p>","PeriodicalId":79405,"journal":{"name":"Journal of inflammation","volume":"45 4","pages":"248-59"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19833210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conserved high-affinity NF-kappa B binding site in the interferon regulatory factor-1 promoter is not occupied by NF-kappa B in vivo and is transcriptionally inactive.","authors":"T Rein,&nbsp;R Schreck,&nbsp;W Willenbrink,&nbsp;W J Neubert,&nbsp;H Zorbas,&nbsp;P A Bäuerle","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The promoter of the interferon regulatory factor-1 (IRF-1) gene contains at position -47 to -38 an evolutionary conserved binding sequence for the inducible transcription factor NF-kappa B. This site is highly homologous to a transcriptionally active site from the MHC class I enhancer. In this study, we show by in vitro assays using purified NF-kappa B that the kappa B motif in the IRF-1 promoter binds the factor specifically and with high affinity, comparable to various other cis-acting kappa B elements. Two copies of the IRF-1 kappa B site fused to the heterologous c-fos promoter conferred induction of a chloramphenicol acetyl transferase (CAT) reported gene in response to stimulation of L929 fibroblasts with various NF-kappa B inducers, such as tumor necrosis factor alpha (TNF alpha) or phorbol 12-myristate 13-acetate (PMA). Mutation of the binding site completely abolished transcriptional inducibility of the heterologous promoter. Surprisingly, the same IRF-1 kappa B motif in context of the homologous IRF-1 promoter was transcriptionally inactive in CAT assays. The very weak induction of the IRF-1 promoter in response to TNF treatment or infection of fibroblasts with Newcastle disease virus (NDV) was barely affected by point mutation of the kappa B site or loss of the site by truncation of the promoter. Analysis of the occupational state of the chromosomal IRF-1 kappa B site by in vivo foot-printing revealed that no footprint was induced over the kappa B motif in the IRF-1 promoter after PMA treatment of L929 fibroblast cells, despite the simultaneous induction of IRF-1 mRNA and NF-kappa B binding activity. Constitutive footprints were detected at a CCAAT and GC-rich region in the promoter. This is the first example of a high-affinity NF-kappa B binding site within a promoter which may not participate in transcriptional regulation under conditions activating NF-kappa B DNA binding and gene expression.</p>","PeriodicalId":79405,"journal":{"name":"Journal of inflammation","volume":"45 4","pages":"269-82"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19833212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of an adenovirally encoded lymphotoxin-beta inhibitor prevents clearance of Listeria monocytogenes in mice.","authors":"R Trüeb,&nbsp;G Brown,&nbsp;C Van Huffel,&nbsp;A Poltorak,&nbsp;M Valdez-Silva,&nbsp;B Beutler","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The lymphotoxin (LT)-beta heterotrimer was recently identified as a molecule containing LT-alpha subunits, tethered to the cell through non-covalent association with an integral plasma membrane protein, derived from the LT-beta gene. Since knockout mutations of the LT-alpha gene yield animals that lack lymph nodes, whereas animals lacking either or both of the receptors for tumor necrosis factor (TNF) and LT-alpha homotrimers have normal lymph nodes, it has been inferred that the association between the LT-beta heterotrimer and its cognate receptor is required for lymph node ontogeny. Similarly, LT-beta and its receptor are thought to be important for development of the spleen. Since LT-alpha deficient mice lack lymph nodes, it is difficult to assess the extradevelopmental contribution of LT-beta to immune competence. To this end, we employed a strategy for the conditional blockade of LT-beta heteromer activity in normal mice. The interaction between LT-beta and its receptor is essential for the destruction of intracellular Listeria monocytogenes.</p>","PeriodicalId":79405,"journal":{"name":"Journal of inflammation","volume":"45 4","pages":"239-47"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19833341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}