Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P80098 (monocyte chemoattractant protein)
 1,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chemokines are thought to play a pivotal role in mediating the selective migration of leukocytes into sites of tissue injury. The local production of chemokines by mesangial cells (MC) has been linked to inflammatory processes within the glomerulus. To study the chemokine biology of human MC, an immortalized human MC line was generated and then chemokine and chemokine receptor expression was examined in response to various proinflammatory stimuli. The results show that human MC have a specific and limited repertoire of chemokine expression. The stimulus-specific regulation of the chemokines monocyte chemoattractant protein- (MCP- 1), regulated upon activation, normal T cell expressed and secreted (RANTES), interleukin-8 (IL-8), and IP-10 was demonstrated using RNase protection assays. Transcripts for the chemokines MIP-1alpha, MIP-1beta, I-309, or lymphotactin could not be detected. The expression of CC chemokine receptors was investigated by reverse transcription-PCR and RNase protection assays. MC stimulated with interferon-gamma (IFN-gamma) expressed mRNA for the chemokine receptor CCR1. The expression could be further increased by activating the cells with a combination of tumor necrosis factor-a (TNF-alpha), IL-1beta, and IFN-gamma. Under these conditions, no mRNA for CCR2, CCR3, CCR4, CCR5, or CCR8 was detected. A comparison of the immortalized human mesangial cells with primary cells showed identical expression patterns of chemokine receptors. To demonstrate functional activity of chemokine receptors expressed by human MC, chemotaxis assays were performed. MC stimulated with a combination of TNF-alpha, IL-1beta, and IFN-gamma, but not unstimulated MC, migrated toward a RANTES gradient. Eotaxin did not enhance the migratory activity of human MC. In summary, a novel human mesangial cell line was established and the pattern of chemokine expression was examined. For the first time, the inducible expression of functionally active CCR1 by human MC was shown.
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PMID:Chemokine and chemokine receptor expression in a novel human mesangial cell line. 1054 Dec 90

Sixteen healthy subjects were intravenously injected with lipopolysaccharide (LPS), once with placebo and once with recombinant human interleukin (IL)-10 (25 microgram/kg), to determine the effect of IL-10 on LPS-induced production of macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and monocyte chemoattractant protein (MCP)-1. LPS induced transient increases in serum MIP-1alpha, MIP-1beta, and MCP-1. Pretreatment with IL-10 inhibited LPS-induced release of MIP-1alpha, MIP-1beta, and MCP-1. In whole blood in vitro, the IL-10-induced inhibition of MIP-1alpha and MIP-1beta release was equally potent in the presence or absence of an anti-tumor necrosis factor (TNF) antibody. Although isolated peripheral blood mononuclear cells produced more MIP-1alpha and MIP-1beta than neutrophils, the latter cells were more sensitive to the inhibiting effect of IL-10. IL-10 attenuates LPS-induced production of CC chemokines in human endotoxemia, whereby in vitro experiments suggest that, in the case of MIP-1alpha and MIP-1beta release, this effect is independent from an inhibitory effect on TNF production.
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PMID:Interleukin 10 inhibits the release of CC chemokines during human endotoxemia. 1066 45

Neonatal animals of some mammalian species are more tolerant to several pulmonary oxidative stress-inducing toxicants than adults. Our initial studies during hyperoxic injury demonstrated a rapid chemokine and cytokine response early in the development of injury in newborn mice, whereas adult mice demonstrated little alteration in cytokine abundance until lethality was imminent. Our hypothesis is that altered response between newborn and adult mice is associated with differential cell injury, rather than alterations in the regulation of the inflammatory response. To test this hypothesis we utilized two distinct models of inducing pulmonary toxicity: ozone (O(3)), which causes epithelial cell injury, and endotoxin, which causes pulmonary inflammation independent of direct epithelial cell injury. C57Bl/6J mice (36 h or 8 wk old) were exposed to O(3) at 1 or 2.5 ppm for 4, 20, or 24 h or to a 10-min inhalation of 10 ng endotoxin per mouse (estimated deposited dose) and were examined 2, 6, or 24 h postexposure. Adult mice displayed increased sensitivity to O(3), as demonstrated by increased abundance of mRNAs encoding eotaxin, macrophage inflammatory protein (MIP)-1alpha, MIP-2, interleukin (IL)-6, and metallothionein (Mt). In newborn mice, only Mt was increased after 4 h of exposure. In contrast, newborn and adult mice responded similarly at 2 h post endotoxin exposure, inducing messages encoding tumor necrosis factor (TNF)-alpha, eotaxin, MIP-1alpha, MIP-1beta, MIP-2, interferon inducible protein (IP)-10, and monocyte chemoattractant protein (MCP)-1. Furthermore, interleukin-6 (IL-6) was increased in adults but not newborns. Similar chemokine and cytokine responses of newborn and adult mice in response to an agent not causing epithelial injury (endotoxin) suggest that altered inflammatory control observed between newborn and adult mice following O(3) exposure is secondary to epithelial cell injury.
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PMID:Newborn mice differ from adult mice in chemokine and cytokine expression to ozone, but not to endotoxin. 1071 25

Sepsis and septic syndrome represent an intense systemic response with multiple physiologic and immunologic abnormalities, leading to multiple organ failure. Recent investigations suggest that the critical conditions are balanced by endogenous cytokines. In the present study, we examined the involvement of endogenous monocyte chemoattractant protein (MCP)-1 in the regulation of cytokine production in tissue/organs in a murine model of acute septic peritonitis induced by cecal ligation and puncture (CLP). Initial studies showed that CLP induced elevated levels of MCP-1 in tissues, such as liver, lung, and kidney. To neutralize endogenous MCP-1, either anti-MCP-1 antibodies or control antibodies were intraperitoneally administered 2 h prior to CLP. Administration of anti-MCP-1 antibodies resulted in a decrease in the level of interleukin (IL)-13 in tissues, while increasing the level of tumor necrosis factor-alpha, compared to control. In addition, anti-MCP-1 treatment decreased the level of IL-12 and, in contrast, increased the level of IL-10 in specific tissues. These findings suggest that endogenous MCP-1 influences the cytokine balance in tissues in favor of anti-inflammatory and immune-enhancing cytokines, probably protecting the host from tissue/organ damage during sepsis.
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PMID:Endogenous MCP-1 influences systemic cytokine balance in a murine model of acute septic peritonitis. 1071 11

Hyperoxic lung injury, believed to be mediated by reactive oxygen species, inflammatory cell activation, and release of cytotoxic cytokines, complicates the care of many critically ill patients. The cytokine tumor necrosis factor (TNF)-alpha is induced in lungs exposed to high concentrations of oxygen; however, its contribution to hyperoxia-induced lung injury remains unclear. Both TNF-alpha treatment and blockade with anti-TNF antibodies increased survival in mice exposed to hyperoxia. In the current study, to determine if pulmonary oxygen toxicity is dependent on either of the TNF receptors, type I (TNFR-I) or type II (TNFR-II), TNFR-I or TNFR-II gene-ablated [(-/-)] mice and wild-type control mice (WT; C57BL/6) were studied in >95% oxygen. There was no difference in average length of survival, although early survival was better for TNFR-I(-/-) mice than for either TNFR-II(-/-) or WT mice. At 48 h of hyperoxia, slightly more alveolar septal thickening and peribronchiolar and periarteriolar edema were detected in WT than in TNFR-I(-/-) lungs. By 84 h of oxygen exposure, TNFR-I(-/-) mice demonstrated greater alveolar debris, inflammation, and edema than WT mice. TNFR-I was necessary for induction of cytokine interleukin (IL)-1beta, IL-1 receptor antagonist, chemokine macrophage inflammatory protein (MIP)-1beta, MIP-2, interferon-gamma-induced protein-10 (IP-10), and monocyte chemoattractant protein (MCP)-1 mRNA in response to intratracheal administration of recombinant murine TNF-alpha. However, IL-1beta, IL-6, macrophage migration inhibitory factor, MIP-1alpha, MIP-2, and MCP-1 mRNAs were comparably induced by hyperoxia in TNFR-I(-/-) and WT lungs. In contrast, mRNA for manganese superoxide dismutase and intercellular adhesion molecule-1 were induced by hyperoxia only in WT mice. Differences in early survival and toxicity suggest that pulmonary oxygen toxicity is in part mediated by TNFR-I. However, induction of specific cytokine and chemokine mRNA and lethality in response to severe hyperoxia was independent of TNFR-I expression. The current study supports the prediction that therapeutic efforts to block TNF-alpha receptor function will not protect against pulmonary oxygen toxicity.
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PMID:Ablation of tumor necrosis factor receptor type I (p55) alters oxygen-induced lung injury. 1078 41

Chemokines may regulate the process of immune cell infiltration that is often found in pancreatic cancer. In this study, we investigated the secretion of the chemokines [interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1, and RANTES (regulated on activation, normal T cell expressed and secreted)] in human pancreatic cancer cell lines. The chemokine secretion in three pancreatic cancer cell lines (PANC-1, MIA PaCa-2, and BxPC-3) was evaluated by enzyme-linked immunosorbent assay (ELISA) and Northern blot, and the activation of nuclear factor-kappaB (NF-kappaB) and NF-IL6 was assessed by an electrophoretic gel mobility shift assay (EMSA). Without any stimulation, IL-8 secretion was detected in all cell lines, and MCP-1 secretion was detected in PANC-1 and MIA PaCa-2 cells. However, RANTES secretion was not detected in all cells. The addition of IL-1beta and tumor necrosis factor (TNF)-alpha strongly enhanced IL-8, MCP-1, and RANTES secretion; these responses were observed at the mRNA level as well as at the protein level. IL-1beta and TNF-alpha induced a rapid activation of nuclear factor (NF)-kappaB in PANC-1 cells, and the increase in chemokine mRNA expression correlated with NF-kappaB activation. The activation of NF-IL6 was modest. A blockade of NF-kappaB activation by TPCK markedly reduced the IL-1beta- and TNF-alpha-induced chemokine gene expression. Our findings indicate that chemokines are produced by pancreatic cancer cells, and suggest that these factors may contribute to the accumulation of tumor-associated immune cells. In addition, the transcriptional activation of chemokine genes in pancreatic cancer cells may be closely associated with NF-kappaB activation.
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PMID:The expression of chemokine genes correlates with nuclear factor-kappaB activation in human pancreatic cancer cell lines. 1088 30

The evaluation of monocytes recruited into the alveolar space under both physiological and inflammatory conditions is hampered by difficulties in discriminating these cells from resident alveolar macrophages (rAMs). Using the intravenous injected fluorescent dye PKH26, which accumulated in rAMs without labeling blood leukocytes, we developed a technique that permits the identification, isolation, and functional analysis of monocytes recruited into lung alveoli of mice. Alveolar deposition of murine JE, the homologue of human monocyte chemoattractant protein (MCP)-1 (JE/MCP-1), in mice provoked an alveolar influx of monocytes that were recovered by bronchoalveolar lavage and separated from PKH26-stained rAMs by flow cytometry. Alveolar recruited monocytes showed a blood monocytic phenotype as assessed by cell surface expression of F4/80, CD11a, CD11b, CD18, CD49d, and CD62L. In contrast, CD14 was markedly upregulated on alveolar recruited monocytes together with increased tumor necrosis factor-alpha message, discriminating this monocyte population from peripheral blood monocytes and rAMs. Thus monocytes recruited into the alveolar air space of mice in response to JE/MCP-1 keep phenotypic features of blood monocytes but upregulate CD14 and are "primed" for enhanced responsiveness to endotoxin with increased cytokine expression.
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PMID:Monocytes recruited into the alveolar air space of mice show a monocytic phenotype but upregulate CD14. 1113 95

Only limited data on cerebrospinal fluid (CSF) HIV-1 RNA responses and markers of local inflammation in CSF during antiretroviral therapy are available. HIV-RNA, soluble tumor necrosis factor (TNF)-receptor (sTNFr)-II, monocyte chemoattractant protein (MCP)-1, and interferon-gamma-inducible protein (IP)-10 were measured in the peripheral blood and CSF of 26 antiretroviral-naive HIV-1-positive patients, who were treated with ritonavir (RTV)/saquinavir (SQV) (n = 5), RTV/SQV/stavudine (d4T; n = 8) or zidovudine (AZT)/lamivudine (3TC)/abacavir/nevirapine/indinavir (n = 13). After 8 to 12 weeks of treatment, CSF HIV-RNA dropped to <400 copies/ml in 1 of 5 patients in the RTV/SQV group, 8 of 8 patients in the RTV/SQV/d4T group, and 9 of 10 patients in the five-drug group. CSF sTNFr-II and IP-10 levels increased in patients with detectable CSF HIV-RNA. However, increases in CSF chemokine and sTNFr-II concentrations were also observed in some patients with good CSF HIV-RNA responses. Moreover, CSF MCP-1 concentrations increased in the whole population after 2 months of treatment. Ongoing residual HIV replication in the central nervous system, which cannot be detected with CSF HIV-RNA measurements, may account for this phenomenon.
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PMID:Increasing cerebrospinal fluid chemokine concentrations despite undetectable cerebrospinal fluid HIV RNA in HIV-1-infected patients receiving antiretroviral therapy. 1114 Dec 42

Leukocyte accumulation during peritonitis is believed to be controlled by chemotactic factors released by resident peritoneal macrophages or mesothelial cells. Recent data indicate, however, that in many tissues fibroblasts play a key role in mediating leukocyte recruitment. We have therefore examined human peritoneal fibroblasts (HPFBs) for the expression and regulation of C-X-C and C-C chemokines. Quiescent HPFBs secreted monocyte chemoattractant protein (MCP)-1 and interleukin (IL)-8 constitutively. This release could be dose-dependently augmented with the pro-inflammatory cytokines IL-1beta and tumor necrosis factor-alpha. Stimulated IL-8 production reached a plateau within 48 hours while MCP-1 continued to accumulate throughout 96 hours. Induction of IL-8 and MCP-1 synthesis by HPFBs was also triggered by peritoneal macrophage-conditioned medium. This effect was partly related to the presence of IL-1beta as demonstrated by IL-1 receptor antagonist inhibition. Pretreatment of HPFBs with actinomycin D or puromycin dose-dependently reduced cytokine-stimulated IL-8 and MCP-1 secretion, which suggested de novo chemokine synthesis. Indeed, exposure of HPFBs to IL-1beta and tumor necrosis factor-alpha produced a significant up-regulation of IL-8 and MCP-1 mRNA. This effect was associated with the rapid induction of nuclear factor-kappaB binding activity mediated through p65 and p50 subunits, and with a transient increase in the mRNA expression for RelB and inhibitory protein kappaB-alpha proteins. These data indicate that peritoneal fibroblasts are capable of generating large quantities of chemokines under a tight control of nuclear factor-kappaB/Rel transcription factors. Thus, peritoneal fibroblast-derived chemokines may contribute to the intraperitoneal recruitment of leukocytes during peritonitis.
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PMID:Synthesis of C-X-C and C-C chemokines by human peritoneal fibroblasts: induction by macrophage-derived cytokines. 1129 May 62

Monocytes recruited from the blood are key contributors to the nature of an immune response. While monocyte recruitment in a subset of immunopathologies has been well studied and largely attributed to the chemokine monocyte chemoattractant protein (MCP)-1, mechanisms mediating such recruitment to other sites of inflammation remain elusive. Here, we showed that localized inflammation resulted in an increased binding of monocytes to perifollicular high endothelial venules (HEVs) of lymph nodes draining a local inflammatory site. Quantitative PCR analyses revealed the upregulation of many chemokines in the inflamed lymph node, including MCP-1 and MIG. HEVs did not express detectable levels of MCP-1; however, a subset of HEVs in inflamed lymph nodes in wild-type (but not tumor necrosis factor [TNF] null mice) expressed MIG and this subset of HEVs preferentially supported monocyte binding. Expression of CXCR3, the receptor for MIG, was detected on a small subset of peripheral blood monocytes and on a significant percentage of recruited monocytes. Most importantly, in both ex vivo and in vivo assays, neutralizing anti-MIG antibodies blocked monocyte binding to inflamed lymph node HEVs. Together, these results suggest that the lymph node microenvironment can dictate the nature of molecules expressed on HEV subsets in a TNF-dependent fashion and that inflammation-induced MIG expression by HEVs can mediate monocyte recruitment.
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PMID:Tumor necrosis factor-dependent segmental control of MIG expression by high endothelial venules in inflamed lymph nodes regulates monocyte recruitment. 1169 3


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