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)

Chemokine production by human retinal pigment epithelium (HRPE) cells is believed to play an important role in ocular inflammation and immune responses. In our previous studies, we demonstrated that glycated human serum albumin (GHSA) strongly stimulates HRPE cells and human corneal keratocytes to produce chemokines. In the present study, we further examined the effects of GHSA on TNF-alpha- and IL-1 beta-induced HRPE IL-8 and monocyte chemoattractant protein (MCP)-1 gene expression and protein secretion in HRPE. At maximally effective concentrations, GHSA (2000 micrograms/ml) potentiated TNF-alpha (20 ng/ml)-stimulated HRPE IL-8 secretion approximately 7-fold. Consistent with the above observations were the time- and dose-dependent increases in the steady-state IL-8 mRNA after coadministration with these two factors, although the half-life of IL-8 mRNA (30 minutes) was not altered by GHSA. In contrast to IL-8, the TNF-alpha-induced HRPE MCP-1 gene expression was only slightly enhanced by GHSA. Moreover, potentiation of HRPE IL-8 generation by GHSA appeared to be selective for TNF-alpha because, under similar conditions, GHSA was unable to enhance the IL-1 beta-stimulated IL-8 gene expression and protein secretion. The IL-1 beta-stimulated HRPE MCP-1 production was also unchanged by GHSA. Collectively, these results suggest specific potentiation of TNF-alpha-induced HRPE IL-8 by human serum albumin that has been glycated either during circulation or locally within tissue. This interaction may be relevant to a variety of ocular diseases involving breakdown of the blood-retinal barrier.
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PMID:Synergy between glycated human serum albumin and tumor necrosis factor-alpha for interleukin-8 gene expression and protein secretion in human retinal pigment epithelial cells. 952 Sep 46

Under a variety of conditions, alveolar macrophages can generate early response cytokines (TNF-alpha, IL-1), complement components, and chemotactic cytokines (chemokines). In the current studies, we determined the requirements for TNF-alpha and the complement activation product C5a in chemokine production in vitro and in vivo. Two rat CXC chemokines (macrophage inflammatory protein (MIP)-2 and cytokine-induced neutrophil chemoattractant (CINC)) as well as three rat CC chemokines (MIP-1alpha, MIP-1beta, and monocyte chemoattractant protein (MCP)-1) were investigated. Chemokine generation in vitro was studied in rat alveolar macrophages stimulated with IgG immune complexes in the absence or presence of Abs to TNF-alpha or C5a. The rat lung injury model induced by IgG immune complex deposition was employed for in vivo studies. Abs to TNF-alpha or C5a were administered intratracheally or i.v., and effects on chemokine levels in bronchoalveolar lavage fluids were quantitated by ELISA. Both in vitro and in vivo studies demonstrated the requirements for TNF-alpha and C5a for full generation of CXC and CC chemokines. In vitro and in vivo blockade of TNF-alpha or C5a resulted in significantly reduced production of chemokines. Supernatant fluids from in vitro-stimulated macrophages revealed by Western blot analysis the presence of C5a/C5adesArg, indicating intrinsic generation of C5a/C5adesArg by alveolar macrophages and explaining the higher efficiency of intratracheal vs i.v. blockade of C5a in reducing chemokine production. These results underscore the central role of both TNF-alpha and C5a, which appear to function as autocrine activators to promote CXC and CC chemokine generation by alveolar macrophages.
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PMID:In vitro and in vivo dependency of chemokine generation on C5a and TNF-alpha. 997 10

Differential chemokine production by colonic epithelial cells is thought to contribute to the characteristic increased infiltration of selected population of leukocytes cells in inflammatory bowel disease. We have previously demonstrated that IL-13 enhances IL-1alpha-induced IL-8 secretion by the colonic epithelial cell line HT-29. We have now explored the C-C chemokine expression and modulation in this system. The combination of TNF-alpha and IFN-gamma was the minimal stimulation required for regulated on activation, normal T cell expressed and secreted (RANTES) and monocyte chemoattractant protein (MCP-1) mRNA expression and secretion by HT-29 cells. The same stimulation induced a stronger IL-8 mRNA expression and secretion. Pretreatment with IL-13 or IL-4, reduced significantly the RANTES, and MCP-1, but not IL-8 mRNA expression and secretion. In contrast, IL-10 had no effect on either MCP-1, or RANTES, or IL-8 generation. Pretreatment of HT-29 cells with wortmannin suggested that the IL-13-induced inhibition of C-C chemokine expression is via activation of a wortmannin-sensitive phosphatidylinositol 3-kinase. These data demonstrate that colonic epithelial cell chemokine production can be differentially regulated by T cell-derived cytokines and suggest an interplay between epithelial cells and T lymphocytes potentially important in the intestinal inflammation.
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PMID:C-X-C and C-C chemokine expression and secretion by the human colonic epithelial cell line, HT-29: differential effect of T lymphocyte-derived cytokines. 1006 68

Bone marrow-derived macrophages (BMM) comprise a population of quiescent cells which can be activated by defined signals. Here, we directly compare the release of chemokines and monokines by BMM raised either in serum-supplemented or in serum-free medium in response to Listeria monocytogenes EGD or Mycobacterium bovis BCG infection. We focused on this issue because there have been several controversial reports on the production of cytokines by BMM due to different in vitro culture conditions. Culture in serum-supplemented medium primed BMM for release of monocyte chemoattractant protein (MCP)-1, interleukin (IL)-6, and IL-12, but had no effect on macrophage inflammatory protein (MIP)-1alpha and tumor necrosis factor (TNF)-alpha production in response to L. monocytogenes infection. After challenge infection with M. bovis, BMM raised and stimulated in serum-supplemented medium secreted higher levels of MCP-1, MIP-1alpha, IL-6, and TNF-alpha but not of IL-12 as compared to BMM cultured and infected in a serum-free medium. The effects of serum could be partially mimicked by interferon-gamma. Because the serum components responsible for BMM priming are undefined, BMM cultured under serum-free conditions provide an appropriate cell population for defining macrophage activating signals.
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PMID:Effect of fetal calf serum on cytokine release by bone marrow-derived macrophages during infection with intracellular bacteria. 1008

Eotaxin potentially plays an integral role in tissue eosinophilia. Inasmuch as Th2-derived cytokine IL-4 has been shown to stimulate eotaxin generation, we investigated here the effect of Th1-derived cytokine IFN-gamma on human eotaxin production. IFN-gamma but not -alpha or -beta potently inhibited tumor necrosis factor (TNF)-alpha-induced eotaxin generation by dermal fibroblasts. The inhibitory effect was unique to eotaxin, because production of IL-8 or monocyte chemoattractant protein (MCP)-1 protein was not affected by the treatment with IFN-gamma. Furthermore, the suppressive effect of IFN-gamma was not cell-type or stimulus specific. The level of eotaxin mRNA increased within 2 h after activation with TNF-alpha and continued to increase up to 72 h. IFN-gamma did not inhibit, but rather augmented the TNF-alpha-induced accumulation of mRNA in the early phase ( approximately 6 h). However, in the later phase, IFN-gamma completely prevented the subsequent elevation of eotaxin mRNA and sustained it at low levels. Although the protective effect of IFN-gamma against allergic inflammation has been assumed to result from its sole regulation of the proliferation of Th2-type T lymphocytes, these results imply that IFN-gamma can also directly act on stromal cells to inhibit eotaxin production and consequently intervene in eosinophil recruitment.
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PMID:Th1-derived cytokine IFN-gamma is a potent inhibitor of eotaxin synthesis in vitro. 1036 Sep 75

The dimensions of man-made mineral fiber whiskers are similar to those of some kinds of asbestos. Thus these mineral fibers raise the concern for potential health hazard for workers exposed in the occupational environments. This study was designed to define acute biological effects of intratracheally administered titanium dioxide whiskers (TO1) compared with nonfibrous titanium dioxide (TOP) and UICC amosite (Ams), and their relations to acute lung inflammation in rats. The observed geometric mean length (microm) and width (microm) and geometric standard deviation are: TO1(2.1[2.0], 0.14[1. 53]); Ams (4.3[3.3], 0.31[1.9]); and TOP (50 nm, 1-2 microm aggregates). Ten-week-old Wistar-Jcl male rats received a single tracheal injection of test materials at doses between 0.05 and 1.0 mg/rat. Control animals were injected with the same volume of saline. Lung tissue and bronchoalveolar lavage (BAL) fluid were collected from rats on days 1, 3, and 7 after administration. In the group injected with TO1, total protein, cytokine-induced neutrophil chemoattractant (CINC)/growth-regulated gene product (GRO), interleukin (IL) 1beta, and tumor necrosis factor (TNF) alpha increased on day 1. Subsequently, total elastolytic activity and fucose levels in BAL increased by day 3. All parameters, except for fucose in BAL, recovered to the normal levels. Animals in the Ams group showed increased total protein and CINC/GRO and decreased total elastolytic activity in a dose-dependent manner on day 1. The fucose level increased on day 3 in the Ams group. All parameters returned to their control levels on day 7. Animals in the TOP group did not show significant changes any of parameters during the experimental period. Gene expression of TNF-alpha and monocyte chemoattractant protein (MCP) 3 in the lung increased dose-dependently in the animals treated with the three materials. The mRNAs for eotaxin and MIP-1alpha were overexpressed in the lung of animals treated with Ams and TO1, while RANTES mRNA was overexpressed dose-dependently in the lung of animals treated with Ams on day 1. Onset of inflammatory response was more rapid in the Ams group than the TO1 group. Recovery of the fucose level in BAL was slower in the TO1 group than in the Ams group, though we observed similar histopathological changes in the lung of animals with TO1 or Ams. We conclude that whisker-induced acute biological effects in the lung may be related to the shape of the whiskers and not to their chemical composition or surface crystal structure, showing biological effects similar to those of UICC amosite.
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PMID:Acute biological effects of intratracheally instilled titanium dioxide whiskers compared with nonfibrous titanium dioxide and amosite in rats. 1038 Jan 63

The murine epidermis contains two types of dendritic cells (DC), Thy-1+ dendritic epidermal T cells (DETC) and Langerhans cells. In this review, we introduce our data obtained using a skin organ culture system to examine the migratory capacity of DETC and Langerhans cells into the epidermis. DETC or Langerhans cells were depleted by topical application ofclobetazole propionate (CP) solution onto the murine ears. CP-treated or untreated ear skin was co-cultured with syngeneic (semi-syngeneic, or allogenic, in experiments with Langerhans cells) epidermal cell suspension. We found (i) that donor DETC or Langerhans cells migrated into the CP-treated epidermis as well as into untreated epidermis, (ii) that leukosialin Ly48 recognized by monoclonal antibody S11 and TNF-alpha strongly inhibited donor Langerhans cell migration into the epidermis. We mention other molecules that may participate in the migration of Langerhans cells such as chemotactic cytokines, monocyte chemoattractant protein (MCP)-1, TGF-beta and skin-homing molecule, cutaneous lymphocyte-associated antigen (CLA) on Langerhans cells.
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PMID:Molecular mechanisms involved in the migration of epidermal dendritic cells in the skin. 1053 94

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

1. The 1,4-dihydropyridine nifedipine is frequently used in the therapy of hypertension and heart failure. In addition, nifedipine has been shown to exert distinct anti-arteriosclerotic effects both in experimental animal models and in patients. In the present study we have investigated the hypothesis that the latter effect of this class of drugs is mediated by an interference with the expression of pro-arteriosclerotic gene products in the vessel wall. Moreover, to elucidate as to whether nifedipine acts via L-type calcium channel blockade, its effects were compared to those of another dihydropyridine, Bay w 9798, which has no calcium-antagonistic properties in concentrations up to 10 microM as verified by superfusion bioassay. 2. Both, nifedipine and Bay w 9798, in concentrations ranging from 0.01 to 1 microM, augmented the interleukin-1beta/tumour necrosis factor-alpha (IL-1beta/TNF-alpha)-induced expression of the inducible isoform of nitric oxide synthase (iNOS) in rat aortic cultured smooth muscle cells (raSMC) 2 - 3 fold, as judged by RT - PCR and Western blot analyses. 3. In contrast, cytokine-induced mRNA expression of monocyte chemoattractant protein 1 (MCP-1) in these cells was down-regulated by more than 60% in the presence of both dihydropyridines, as judged by RT - PCR and Northern blot analyses. 4. Nuclear run-on assays and incubation with the transcription-terminating drug actinomycin D revealed that both drugs acted at the level of mRNA synthesis rather than stability. 5. These findings suggest that 1,4-dihydropyridines such as nifedipine affect the expression of both potentially pro-arteriosclerotic (MCP-1) and anti-arteriosclerotic (iNOS) gene products in the vessel wall at the level of transcription, and that these effects are unrelated to their calcium channel-blocking properties.
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PMID:Modulation by dihydropyridine-type calcium channel antagonists of cytokine-inducible gene expression in vascular smooth muscle cells. 1072 64

Ischemia-reperfusion injury (IRI) is a major cause of renal dysfunction in both native kidneys and renal allografts. To broaden our understanding of the inflammatory mediators involved in IRI, we used multi-probe RNase protection assays to examine the expression of 26 different cytokine genes in a murine model of renal IRI. We observed that, in addition to up-regulation of IL-1beta and to a lesser extent TNF-alpha, IRI was associated with an intense and sustained up-regulation of three gp130-signaling cytokines, IL-6, IL-11, and leukemia inhibitory factor (LIF), as well as with up-regulation of the neutrophil chemotactic and activating mediator macrophage inflammatory protein (MIP)-2. Macrophage colony-stimulating factor (M-CSF) and monocyte chemoattractant protein (MCP)-1 were also moderately up-regulated after IRI, whereas mRNA levels of several other inflammatory mediators including IL-1alpha, IL-2, IL-4, interferon (IFN)-gamma, GM-CSF, and RANTES were minimally increased or remained undetectable. These findings identify MIP-2 as an attractive target for inhibition of leukocyte recruitment in renal IRI and also suggest a potentially novel role for gp130-mediated signals in IRI.
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PMID:Prominent and sustained up-regulation of gp130-signaling cytokines and the chemokine MIP-2 in murine renal ischemia-reperfusion injury. 1075 57


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