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)

IL-11 is a pleiotropic cytokine that induces tissue remodeling with subepithelial fibrosis when expressed in the airway. Its effects on the Th2-dominated airway inflammation that is characteristic of asthma, however, are poorly understood. To characterize the effects of IL-11 on Th2 tissue inflammation, we compared the inflammatory responses elicited by OVA in sensitized mice in which IL-11 is overexpressed in a lung-specific fashion (CC10-IL-11) with that in transgene- wild-type littermate controls. Transgene- and CC10-IL-11 transgene+ mice had comparable levels of circulating Ag-specific IgE after sensitization. OVA challenge of sensitized transgene- mice caused airway and parenchymal eosinophilic inflammation, Th2 cell accumulation, and mucus hypersecretion with mucus metaplasia. Exaggerated levels of immunoreactive endothelial cell VCAM-1, mucin (Muc) 5ac gene expression and bronchoalveolar lavage and lung IL-4, IL-5, and IL-13 protein and mRNA were also noted. In contrast, OVA challenge in CC10-IL-11 animals elicited impressively lower levels of tissue and bronchoalveolar lavage inflammation, eosinophilia, and Th2 cell accumulation, and significantly lower levels of VCAM-1 and IL-4, IL-5, and IL-13 mRNA and protein. IL-11 did not cause a comparable decrease in mucus hypersecretion, Muc 5ac gene expression, or the level of expression of RANTES, monocyte chemoattractant protein-2, or monocyte chemoattractant protein-3. In addition, IL-11 did not augment IFN-gamma production demonstrating that the inhibitory effects of IL-11 were not due to a shift toward Th1 inflammation. These studies demonstrate that IL-11 selectively inhibits Ag-induced eosinophilia, Th2 inflammation, and VCAM-1 gene expression in pulmonary tissues.
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PMID:IL-11 selectively inhibits aeroallergen-induced pulmonary eosinophilia and Th2 cytokine production. 1092 10

In this study, we demonstrate that Dermatophagoides farinae (Der f), a major source of airborne allergens, but not OVA, could rapidly activate mast cells in mice. This was indicated by an elevation of serum mouse mast cell protease 1, a mast cell-specific proteinase, as early as 30 min after intratracheal challenge. Administration of sodium cromoglycate (40 mg/kg, i.p., 1 h before Der f instillation), a mast cell stabilizer, not only suppressed acute mouse mast cell protease 1 production but also attenuated the allergic airway inflammation provoked by repetitive Der f challenge in mice (five times at 1-wk interval). Der f induced the expression of mRNA for TNF-alpha, IL-1beta, IL-4, IL-6, IL-9, and IL-13 in mastocytoma P815 cells and stimulated both P815 cells and bone marrow-derived mast cells to produce IL-4, IL-6, and TNF-alpha in a dose- and time-dependent manner. Cycloheximide as well as sodium cromoglycate blocked the Der f-induced IL-4 production, indicating a de novo protein synthesis process. Supernatants of Der f-stimulated mast cells chemoattracted monocytes and T lymphocytes; they up-regulated the expression of costimulatory B7 molecules, eotaxin, RANTES, monocyte chemoattractant protein 1, and IFN-inducible protein 10 mRNA of alveolar macrophages; they supported PHA-induced T cell proliferation; and they promoted Th2 cell development. Our data indicate that mast cells may be an important cell type during the initiation of Der f sensitization in the airway by modulating the function of alveolar macrophages and T cells.
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PMID:Activation of mast cells is essential for development of house dust mite Dermatophagoides farinae-induced allergic airway inflammation in mice. 1450 Jun 82

Cerebral palsy (CP) is a major neurodevelopmental disability in childhood. An association between intrauterine infection and CP has been reported. We examined the relationship between inflammatory mediators in cord serum and CP in term and preterm children. Regional multicenter study was conducted on 19 CP children and 19 gestation-matched paired controls. CP children (n = 27) were further compared with controls of similar gestation at birth (n = 25). Serum levels of 78 protein mediators were analyzed. Eleven analytes correlated with the length of gestation both in cases and controls. In paired analysis, B-lymphocyte chemoattractant, ciliary neurotrophic factor, epidermal growth factor, interleukin (IL)-5, IL-12, IL-13, IL-15, macrophage migration inhibitory factor, monocyte chemoattractant protein-3, monokine induced by interferon gamma, and tumor necrosis factor-related apoptosis-inducing ligand were higher in children with CP (p < or = 0.05). Preterm infants with CP showed higher epidermal growth factor and lower levels of granulocyte-macrophage colony-stimulating factor, IL-2, macrophage-derived chemokine, and pulmonary and activation-regulated chemokine than their paired controls. Inflammatory mediators and growth factors serve as a footprint of the fetal response to an insult manifesting after birth as a permanent brain damage. The cytokine patterns at birth differ between premature and term infants who develop CP.
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PMID:Cerebral palsy is characterized by protein mediators in cord serum. 1475 17

Seminal fluid is known to be responsible for orchestrating mating-induced immunomodulation. Central to this process are numerous cytokines that modulate uterine leukocyte recruitment and trafficking. Despite this, a comprehensive analysis of the cytokine profile of murine seminal fluid is lacking. This study addressed this issue by using multiplex immunoassays to characterise the profile of interleukin (IL)-1alpha , IL-1beta , IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12 (p40), IL-12 (p70), IL-13, IL-17, eotaxin, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), interferon (IFN)-gamma, keratinocyte-derived chemokine (KC), monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1alpha , MIP-1beta , regulated upon activation normal T-cell expressed and secreted (RANTES), and tumour necrosis factor (TNF)-alpha in fluid drawn from the seminal vesicles of single mice (n = 18). Their levels and ratios were compared with those found in serum. IL-1alpha , IL-1beta , IL-2, IL-5, IL-9, IL-12 (p40), IL-12 (p70), IL-13, IL-17, GM-CSF, IFN-gamma, MCP-1 and TNF-alpha levels were significantly higher in serum; IL-4, G-CSF, eotaxin, KC and RANTES exhibited the opposite trend. Based on these findings, we propose a model of mating-induced immunomodulation that implicates seminal eotaxin, RANTES and MIP-1alpha in the relocation and concentration of extravasated migrating endometrial eosinophils to the luminal epithelium. Furthermore, KC may participate in uterine neutrophil chemotaxis and activation. Eotaxin and MIP-alpha , together with IL-1beta and IL-9, may also enhance further cytokine synthesis for endometrial antigen-presenting cell recruitment for processing paternal ejaculate antigens. IL-4 and G-CSF could also minimise deleterious cell-mediated immunity and modulate IFN-gamma production, thereby supporting the establishment of pregnancy.
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PMID:Multiplex determination of murine seminal fluid cytokine profiles. 1651 4

A severe burn leads to hypermetabolism and catabolism resulting in compromised function and structure of essential organs. The massive release of cytokines is implicated in this hypermetabolic response. The aim of the present study was to compare cytokine expression profiles from severely burned children without signs of infections or inhalation injury (n = 19) to the cytokine profiles from normal, noninfected, nonburned children (n = 14). The Bio-Plex suspension array system was used to measure the concentration of 17 cytokines. The expression of proinflammatory and anti-inflammatory cytokines was maximal during the first week after thermal injury. Significant increases were measured for 15 mediators during the first week after thermal injury: interleukin (IL) 1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 p70, IL-13, IL-17, interferon gamma, monocyte chemoattractant protein 1, macrophage inflammatory protein 1beta, and granulocyte colony-stimulating factor (P < 0.05). Granulocyte-macrophage colony-stimulating factor was significantly increased during the second week after burn (P < 0.05). Within 5 weeks, the serum concentrations of most cytokines decreased, approaching normal levels. When compared with the cytokine levels measured in normal children, a total of 16 cytokines were significantly altered (P < 0.05). After severe burn, a specific cytokine expression profile is observed in patients without complications such as inhalation injury or sepsis. The cytokine concentrations decrease during 5 weeks after burn but remain elevated over nonburned values. Furthermore, the elevation in most serum cytokine levels during the first week after burn may indicate a potential window of opportunity for therapeutic intervention.
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PMID:Cytokine expression profile over time in severely burned pediatric patients. 1678 92

Cytokines govern uterine immunology and embryo receptivity and are increasingly recognized for their embryotrophic roles. While supplementing culture media with cytokines may improve embryo development/viability in vitro, little is known about their physiological profiles in vivo, and hence which are likely to be uterine immunoregulators and embryotrophins. Therefore, this study profiled 23 cytokines in uterine fluid and serum from individual naturally cycling estrous mice. Samples were analyzed by fluid-phase multiplex immunoassays for interleukin (IL)-1alpha, IL-1beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, IL-12 (p40), IL-12 (p70), IL-13, IL-17, eotaxin, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), interferon (IFN)-gamma, keratinocyte-derived chemokine (KC), monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1alpha MIP)-1beta regulated upon activation, normal T-cell expressed and secreted (RANTES) and tumor necrosis factor (TNF)-alpha. There was a marked divergence in cytokine concentrations between uterine fluid and serum. The former was dominated by G-CSF, eotaxin, KC and IL-1alpha, and had significantly higher levels of IL-1beta, IL-2, IL-3, IL-4, IL-6, IL-9, GM-CSF, MIP-1alpha, MIP-1beta and RANTES. Serum had significantly higher IL-12 (p40), IL-12 (p70), IL-17 and IFN-gamma concentrations. No significant differences in IL-5, IL-10, IL-13, MCP-1 or TNF-alpha profiles were noted. These data indicated a strict compartmentalization of uterine cytokines, with G-CSF as a major cytokine at estrous. Results are discussed with respect to immune cell function, post-coital paternal antigen processing, estrous cyclicity, and endometrial angiogenesis, cell turnover and differentiation.
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PMID:Uterine and serum cytokine arrays in the mouse during estrus. 1696 1

Low-dose diesel exhaust particle (DEP) exposure induces airway inflammation and exaggerates asthmatic responses in mice, but it is unclear whether strains differ in their susceptibility to adverse effects from low-dose DEP exposure. The authors used BALB/c and C57BL/6 mouse strains to search for genetically based differences in response to low-dose DEP (100 microg/m(3)) exposure in terms of airway inflammatory response. The macrophage count in bronchoalveolar lavage (BAL) fluid soon after DE exposure began was significantly greater in C57BL/6 mice (P < .05) than that in BALB/c mice. The count did not increase significantly in BALB/c mice until later. Heme oxygenase-1 (HO-1) mRNA expression and protein production in lung tissues soon after exposure began were more marked in BALB/c mice than in C57BL/6 mice, but the reverse was true later on. The increases in interleukin (IL)-1beta and interferon (IFN)-gamma levels in BAL fluid after DE exposure were significant only in BALB/c mice; there were significantly increases in monocyte chemoattractant protein (MCP)-1, IL-12, IL-10, IL-4, and IL-13 in both strains, but these were more marked in C57BL/6 mice. These interstrain differences in airway inflammatory response after DE exposure were significantly attenuated by antioxidant N-acetylcysteine (NAC) treatment. Changes in airway hyperresponsiveness were independent of the airway inflammation induced by low-dose DEP. Thus, in BALB/c mice, innate immunity may play a central role in DE exposure response, whereas in C57BL/6 mice Th2-dominant responses play a central role. Low-dose DEP exposure induces airway inflammatory responses that differ among strains, and these differences may be caused by differences in sensitivity to oxidative stress.
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PMID:Airway inflammatory responses to oxidative stress induced by low-dose diesel exhaust particle exposure differ between mouse strains. 1762 Jan 85

The authors used BALB/c and C57BL/6 mouse strains to search for genetically based differences in response to prolonged (6 months) low-dose (100 microg/m3) diesel exhaust particle (DEP) exposure from birth in terms of airway inflammatory responses. Histopathological assessment showed that inflammatory cells infiltrated the perivascular areas only in C57BL/6 mice. The count of DEP-laden alveolar macrophages in bronchoalveolar lavage (BAL) fluid was significantly greater in BALB/c mice (P < .05) than in C57BL/6 mice. The lymphocyte and eosinophil count in BAL fluid was significantly greater in C57BL/6 mice (P < .05) than in BALB/c mice. Immunoglobulin (Ig) IgG1 and IgG2 levels in serum, and the monocyte chemoattractant protein (MCP)-1 level in BAL fluid were significantly greater in BALB/c mice than in C57BL/6 mice. The interleukin (IL)-12 level in BAL fluid was significantly greater in C57BL/6 mice than in BALB/c mice, but the IL-13 level in BAL fluid was significantly less in BALB/c mice than in C57BL/6 mice. Glutathione S-transferase (GST) mRNA expression and protein production in lung tissues were significantly lower in C57BL/6 mice than in BALB/c mice, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) level in the lung tissues were significantly greater in C57BL/6 mice than in BALB/c mice. In conclusion, prolonged low-dose DEP exposure induces airway inflammatory responses that differ remarkably among mouse strains; these differences are caused by differences in the host defense response to the oxidative stress induced by DEP exposure and may be useful in the development of biomarkers.
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PMID:Airway inflammatory responses to oxidative stress induced by prolonged low-dose diesel exhaust particle exposure from birth differ between mouse BALB/c and C57BL/6 strains. 1830 22

An immunostimulatory extract based on the medicinal mushroom Agaricus blazei Murill (AbM) has been shown to stimulate mononuclear phagocytes in vitro to produce pro-inflammatory cytokines, and to protect against lethal peritonitis in mice. The present aim was to study the effect of AbM on release of several cytokines in human whole blood both after stimulation ex vivo and in vivo after oral intake over several days in healthy volunteers. The 17 signal substances examined were; T helper 1 (Th1) cytokines [interleukin (IL)-2, interferon (IFN)-gamma and IL-12], T helper 2 cytokines (IL-4, IL-5 and IL-13), pleiotropic (IL-7, IL-17), pro-inflammatory [IL-1beta, IL-6, tumour necrosis factor (TNF)-alpha (mainly produced by Th1 cells)]--and anti-inflammatory (IL-10) cytokines, chemokines [IL-8, macrophage inhibitory protein (MIP)-1beta and monocyte chemoattractant protein (MCP)-1] and leukocyte growth factors [granulocyte colony-stimulating factor (G-CSF), granulocyte/macrophage colony stimulating factor]. After stimulation of whole blood ex vivo with 0.5-5.0% of a mushroom extract, AndoSan mainly containing AbM, there was a dose-dependent increase in all the cytokines studied, ranging from two to 399-fold (TNF-alpha). However, in vivo in the eight volunteers who completed the daily intake (60 ml) of this AbM extract for 12 days, a significant reduction was observed in levels of IL-1beta (97%), TNF-alpha (84%), IL-17 (50%) and IL-2 (46%). Although not significant, there was a trend towards reduced levels for IL-8, IFN-gamma and G-CSF, whilst those of the remaining nine cytokines tested, were unaltered. The discrepant results on cytokine release ex vivo and in vivo may partly be explained by the antioxidant activity of AbM in vivo and limited absorption of its large, complex and bioactive beta-glucans across the intestinal mucosa to the reticuloendothelial system and blood.
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PMID:Effect of an extract based on the medicinal mushroom Agaricus blazei murill on release of cytokines, chemokines and leukocyte growth factors in human blood ex vivo and in vivo. 1928 36

Macrophages are heterogeneous immune cell populations that include classically activated and alternatively activated (M2) macrophages. We examined the anti-inflammatory effect of ANG II type 1 receptor (AT(1)R) blocker (ARB) on glomerular inflammation in a rat model of anti-glomerular basement membrane (GBM) glomerulonephritis (GN). The study focused on infiltrating CD8(+) and CD4(+) cells and macrophages, as well as the heterogeneity of intraglomerular macrophages. Wistar-Kyoto rats were treated with high-dose olmesartan (3 mg.kg(-1).day(-1)), low-dose olmesartan (0.3 mg.kg(-1).day(-1)), or vehicle (control) 7 days before induction of anti-GBM GN. Control rats showed mainly CD8(+) cells and ED1(+) macrophages, with a few CD4(+) cells infiltrating the glomeruli. Necrotizing and crescentic glomerular lesions developed by day 7 with the increase of proteinuria. AT(1)R was expressed on CD8(+) and CD4(+) cells and on ED1(+) macrophages. Low-dose ARB had no anti-inflammatory effects in anti-GBM GN. However, high-dose ARB reduced glomerular infiltration of CD8(+) cells and ED1(+) macrophages and suppressed necrotizing and crescentic lesions by days 5 to 7 (P < 0.05). In addition, high-dose ARB reduced the numbers of ED3(+)-activated macrophages, suppressed glomerular TNF-alpha and IFN-gamma production, and downregulated M1-related chemokine and cytokines (monocyte chemoattractant protein type 1, IL-6, and IL-12). High-dose ARB also enhanced ED2(+) M2 macrophages by day 7 with upregulation of glomerular IL-4 and IL-13 and augmented CCL17, IL-1 receptor antagonist, and IL-10. We concluded that high-dose ARB inhibits glomerular inflammation by increasing the numbers of M2 macrophages and upregulation of anti-inflammatory cytokines and by suppressing M1 macrophage development with downregulation of M1-related proinflammatory cytokines.
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PMID:ANG II receptor blockade enhances anti-inflammatory macrophages in anti-glomerular basement membrane glomerulonephritis. 2013 Jan 23


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