Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.59 (MIP)
 4,906 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytokine and chemokine responses during anamnestic type-1 and type-2 lung granuloma formation were evaluated in mice at 6,12,18 and 24-months of age. Lesions were induced by embolizing Sepharose beads coupled to Mycobacterium bovis purified protein derivative or soluble Schistosoma mansoni egg antigens. Type-1 inflammation was reduced by 18 months, whereas type-2 granulomas not until 24 months of age. In type-1 draining lymph nodes cultures, interferon-gamma (IFNgamma) declined to a nadir by 18, and then partly recovered at 24 months. In contrast, IL-4 was not significantly impaired in type-2 cultures until 24 months. Type-1 and 2 node cultures also displayed decreased IL-13, but paradoxically enhanced IL-5 production at 24 months. Chemokine transcripts in granulomatous lungs displayed age-related alterations. In the type-1 response, CXCL9 (monokine-induced by IFNgamma) declined with age then partly recovered at 24 months parallelling lymph node IFNgamma levels. Transcripts for MIP-2/CXCL2, IP-10/CXCL10, MCP-1/CCL2, and MCP-5/CCL12 increased at 24 months. In the type-2 response MCP-1/CCL2, MCP-3/CCL7, MCP-5/CCL12 and TARC/CCL17 collapsed at 24 months paralleling local IL-4 transcript levels, yet some chemokine transcripts such as KC/CXCL1 and eotaxin/CCL11 were unaffected. These findings suggest that cytokine and chemokine responses degrade differentially with age shifting Th1/Th2 crossregulatory pressures and local expression of chemokines.
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PMID:Differential effects of ageing on cytokine and chemokine responses during type-1 (mycobacterial) and type-2 (schistosomal) pulmonary granulomatous inflammation in mice. 1174 43

C-C chemokines are essential factors in the recruitment and activation of leukocytes from the circulation into inflamed tissue and may play a role in ischemia-induced myocardial injury and left ventricular remodeling after acute myocardial infarction (AMI). We investigated the kinetics of three major C-C chemokines, macrophage chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1 alpha (MIP-1 alpha), and regulated on activation normally T cell expressed and secreted (RANTES), in the sera of AMI patients and correlated the findings with the severity of the disease. Serum levels of C-C chemokines were determined in 35 AMI patients by ELISA assays serially during the first week of hospitalization and 1 month after hospital admission. Patients (n = 18) with uncomplicated AMI (Killip class I) were classified as group A, patients (n = 17) with AMI complicated by heart failure manifestations (Killip classes II and III) were classified as group B, and 15 age-matched and sex-matched volunteers were used as healthy controls. A sustained increase in serum C-C chemokines was observed in both AMI groups during the 7-day hospitalization period. Peaks of these inflammatory factors were significantly higher in group B than in group A (MCP-1, 295 +/- 11 vs. 203 +/- 9 pg/ml, p < 0.01; MIP-1 alpha, 30 +/- 1 vs. 24 +/- 2 pg/ml, p < 0.05; RANTES, 32 +/- 2 vs. 16 +/- 1 ng/ml, p < 0.01) and healthy controls (MCP-1, 125 +/- 7 pg/ml, p < 0.001; MIP-1 alpha, 14 +/- 1 pg/ml, p < 0.001; RANTES, 12 +/- 1 ng/ml, p < 0.001). In group B, significant correlations were found between the peak of MCP-1 and the peak of C-reactive protein levels (r = 0.55, p < 0.02) as well as wedge pressure (r = 0.40, p < 0.05). In the same group, the peak of MIP-1 alpha levels was also significantly correlated with the peak of serum creatine kinase-myocardial band (MB) (r = 0.51, p < 0.04) and left ventricular ejection fraction (LVEF) (r = -0.45, p < 0.05). After 1 month, AMI patients (n = 14) with severe left ventricular dysfunction (LVEF < or = 35%) exhibited significantly higher levels of C-C chemokines (all p < 0.05) than the other AMI patients (n = 21) (LVEF > 35%). A significant correlation was found between MIP-1 alpha levels and left ventricular end-diastolic diameter (r = 0.47, p < 0.03) in this patient population. In conclusion, we have detected a significant elevation of major C-C chemokines during the course of AMI, with the highest levels in patients with AMI complicated by heart failure manifestations and severe left ventricular dysfunction. The elevation of these chemotactic inflammatory factors may actively contribute to the pathophysiology of the disease and the subsequent left ventricular remodeling.
J Interferon Cytokine Res 2002 Feb
PMID:Serum profiles of C-C chemokines in acute myocardial infarction: possible implication in postinfarction left ventricular remodeling. 1191 5

The influx of neutrophils into tissues in response to inflammatory stimuli involves C-X-C chemokines. Interleukin-1 (IL-1) stimulates chemokine production in vitro, but its role in vivo on chemokine production is not as clearly understood. We hypothesized that IL-1 mediates in vivo tissue C-X-C chemokine production induced by systemic lipopolysaccharide (LPS). IL-1 activity was blocked by IL-1 receptor antagonist (IL-1Ra). Rats were injected with Salmonella typhi LPS (0.5 mg/kg) with and without prior administration of IL-1Ra. Cytokine-induced neutrophil chemoattractant-1 (CINC-1) and macrophage inflammatory protein-2 (MIP-2) protein and mRNA levels, tissue neutrophil accumulation, and indices of organ injury were measured. LPS administration resulted in increased plasma, lung, and liver IL-1beta that was decreased by Il-1Ra. LPS also induced an increase in plasma, lung, and liver CINC-1 and MIP-2 protein and mRNA. However, IL-1Ra had no effect on LPS-induced plasma or lung tissue CINC-1 levels. In contrast, IL-1Ra pretreatment did significantly decrease CINC-1 protein expression in the liver (45% decrease) and MIP-2 protein expression in plasma (100% decrease), lung (72% decrease) and liver (100% decrease) compared to LPS- treated controls. Steady-state mRNA levels by Northern blot analysis of both CINC-1 and MIP-2 in lung and liver were similar to the protein findings. Pretreatment with IL-1Ra also resulted in a 47% and 59% decrease in lung and liver neutrophil accumulation, respectively, following LPS. In addition, indices of both lung and liver injury were decreased in animals pretreated with IL-1Ra. In summary, LPS induces IL-1beta and MIP-2 expression in the lung and liver, both of which are IL-1 dependent. Although lung neutrophil accumulation in both lung and liver after LPS is also IL-1 mediated, lung CINC-1 levels were unaffected by IL-1Ra. These data suggest that IL-1 regulates tissue chemokine expression and neutrophil accumulation after LPS.
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PMID:IL-1 regulates in vivo C-X-C chemokine induction and neutrophil sequestration following endotoxemia. 1198 46

Cigarette smoking causes inflammation mainly confined to the airway and lung. Nicotine is one of the primary constituents in cigarette smoke. Alveolar macrophages apparently play a pivotal role in mediating pulmonary inflammation via the production of chemokines. Macrophage inflammatory protein-1 alpha (MIP-1 alpha), a member of CC chemokines, has been shown to contribute to monocyte/macrophage and neutrophil chemotaxis and activation. Our previous work demonstrated that MIP-1 alpha mRNA expression in macrophages is induced by a variety of stimuli. In the present study, we further investigate whether nicotine can regulate the gene expression of MIP-1 alpha in macrophages and determine the mechanism leading to increased expression. A rat alveolar macrophage (RAM) cell line, NR8383, was treated with nicotine at a dose of 3.1, 31, 310 microM, or 3.1 mM. Northern blot analysis showed that the induction of MIP-1 alpha mRNA expression was dose-dependent. To define the time course of the inflammatory response, RAM cells were exposed to 31 microM nicotine, MIP-1 alpha mRNA was induced as early as 1 h after treatment, was maximally expressed at 4 and 6 hours, and reduced by 8 hours. Western blot analysis demonstrated a single band with an estimated molecular weight of 10 kD for MIP-1 alpha which was induced after nicotine treatment, suggesting that expression of MIP-1 alpha mRNA could reflect in protein synthesis. In addition. the increase in MIP-1 alpha mRNA expression induced by nicotine was attenuated by co-treatment with the antioxidant N-acetylcysteine (NAC), at doses of 10 and 20 mM, suggesting that the induction of MIP-1 alpha mRNA is mediated via the generation of reactive oxygen species (ROS). To further investigate transcriptional regulation of the MIP-1 alpha gene expression, RAM cells were exposed to nicotine. MIP-1 alpha mRNA levels were significantly increased in nuclear RNA preparations, indicating that transcriptional activation is involved in increased expression of MIP-1 alpha mRNA. Moreover, we performed RNA decay assay by measuring the half-life of MIP-1 alpha mRNA. Treatment of RAM cells with the transcriptional inhibitor actinomycin D following exposure to nicotine revealed that the half-life of MIP-1 alpha mRNA was markedly increased by nicotine treatment, supporting a role of post-transcriptional stabilization in MIP-1 alpha gene expression. These observations indicate that nicotine can induce MIP-1 alpha mRNA expression and protein synthesis in RAM cells, mediating, at least in part, via the generation of ROS. In addition, the increase in MIP-1 alpha mRNA level involves, both transcriptional activation and post-transcriptional stabilization.
Eur Cytokine Netw
PMID:Expression and regulation of the macrophage inflammatory protein-1 alpha gene by nicotine in rat alveolar macrophages. 1210 Oct 81

Macrophage inflammatory protein-1alpha (MIP-1alpha) and MIP-1beta are highly related members of the CC chemokine subfamily. Despite their structural similarities, MIP-1alpha and MIP-1beta show diverging signaling capacities. Depending on the MIP-1 subtype and its NH(2)-terminal processing, one or more of the CC chemokine receptors CCR1, CCR2, CCR3 and CCR5 are recognized. Since both human MIP-1alpha subtypes (LD78alpha and LD78beta) and MIP-1beta signal through CCR5, the major co-receptor for M-tropic HIV-1 strains, these chemokines are capable of inhibiting HIV-1 infection in susceptible cells. In this review, different aspects of human and mouse MIP-1alpha and MIP-1beta are discussed, including their protein and gene structures, their regulated production, their receptor usage and biological activities and their role in several pathologies including HIV-1 infection.
Cytokine Growth Factor Rev 2002 Dec
PMID:Macrophage inflammatory protein-1. 1240 80

Although adjuvants are essential for the initiation of experimental autoimmune diseases, their precise contribution to the pathological manifestations is still poorly understood. Experimental autoimmune thyroiditis (EAT) is interesting in that respect because it can be initiated with the help of two different adjuvants Freund's complete or LPS which may initiate independent pathogenic pathways. In the present study, we have compared Freund's-induced versus LPS-induced EAT with respect to their dependence upon CD8+ T cells, which are considered as major actors in the pathogenesis of thyroiditis. Our results reveal that whereas CD8+ T cells are mandatory in the Freund's model, they can be bypassed in the LPS model. On the basis of this finding, we have examined the possibility that LPS may act directly upon in vitro cultured thyrocytes with no intermediate cell stages. Indeed, LPS triggers transcription and protein synthesis of several chemokines such as MIP-3alpha, RANTES, MCP-1 or TARC. Thus, beside enhancing the immunogenicity of autoantigens, probably via antigen trafficking and presentation, adjuvants such as LPS directly interact with the target organ through synthesis and release of powerful T cell attractants that facilitate its lymphocytic infiltration.
Eur Cytokine Netw
PMID:LPS and Freund's adjuvant initiate different inflammatory circuits in experimental autoimmune thyroiditis. 1279 14

Activation of the lymphotoxin beta-receptor (LTbetaR), a member of the tumor necrosis factor receptor family, plays a crucial role in lymphoid organogenesis and tumor development. Lymphotoxin alpha(1)beta(2) (LTalpha(1)beta(2)) and LIGHT have been identified as membrane anchored ligands for the LTbetaR. While LTbetaR is expressed on a wide range of cell types e.g. fibroblasts and monocytes, the ligands are expressed only on activated lymphocytes and NK cells. In order to characterize LTbetaR expression and the biological consequences of LTbetaR activation rat anti-mouse LTbetaR monoclonal antibodies were generated. These antibodies recognized a mouse LTbetaR-Ig fusion protein as well as endogenous LTbetaR on a variety of mouse fibroblast and fibrosarcoma cell lines. Specificity was demonstrated by the lack of binding to LTbetaR-deficient embryonic fibroblasts. Competitive binding studies revealed that three different epitopes were recognized by the monoclonal antibodies. Two of the monoclonals activated the LTbetaR and induced activation of NFkappaB and secretion of MIP-2 and IL-6 in L929 mouse fibroblast cells. MIP-2 and IL-6 secretion was NFkappaB-dependent because IkappaB-transfected cells released significantly reduced amounts of both mediators.
Eur Cytokine Netw
PMID:Activation of the lymphotoxin-beta receptor induces NFkappaB-dependent interleukin-6 and MIP-2 secretion in mouse fibrosarcoma cells. 1295 91

Chemokines (chemoattractant cytokines) are key players in the initiation of inflammatory cell accumulation in the central nervous system (CNS). Mechanisms leading to upregulation of chemokines in CNS pathologic conditions remain largely unknown. Numerous in vitro studies showed that inflammatory cytokines stimulate cultured CNS cells to produce chemokines. The main goal of this study was to analyze if an individual proinflammatory cytokine is sufficient to upregulate the chemokine system in the adult CNS in vivo. We analyzed CC chemokine ligand and receptor expression in brains from two different strains of mice (SJL and BALB) after stereotaxic, intracerebral injection of tumor necrosis factor-alpha (TNF-alpha). In both strains, we detected similarly increased expression of chemokines RANTES/CCL5, macrophage inflammatory protein-1alpha (MIP-1alpha)/CCL3, MIP-1beta/CCL4, and MIP-2, as well as chemokine receptors CCR1, CCR2, and CCR5. Interestingly, we did not observe parenchymal leukocyte infiltrates after local TNF-alpha delivery. This observation shows that upregulation of chemokines by TNF-alpha is not sufficient to cause accumulation of leukocytes in the CNS parenchyma in both strains of mice.
J Interferon Cytokine Res 2003 Aug
PMID:TNF-alpha microinjection upregulates chemokines and chemokine receptors in the central nervous system without inducing leukocyte infiltration. 1367 34

Dendritic cells (DC) are potent antigen - presenting cells that can orientate the immune response towards a Th1 or a Th2 type. DC produce chemokines that are involved in the recruitment of either Th1 cells, such as IP10 (CXCL10), Th2 cells such as TARC (CCL17) and MDC (CCL22), or non-polarized T cells such as RANTES (CCL5) and MIP-lalpha (CCL3). We investigated whether monocyte-derived DC (MD-DC) generated from healthy donors or from patients sensitive to Dermatophagoides pteronyssinus (Dpt) and exposed to the cysteine-protease Der p 1(allergen of Dpt), could upregulate the expression of chemokines involved in type 1 or type 2 T cell recruitment. MD-DC were pulsed with either Der p 1 or with LPS as the control and the chemokines produced were evaluated using ELISA and chemotaxis assays. Der p 1-pulsed DC from allergic patients showed increased TARC (CCL17) and MDC (CCL22) production without modifying IP-10 (CXCL10) release. Der p 1-pulsed DC from healthy donors showed only increased IP-10 (CXCL10) secretion. RANTES (CCL5) and MIP-lalpha (CCL3) production were similarly increased when DC were from healthy or allergic donors. The selective Th2 clone recruitment activity of supernatants from Der p 1-pulsed DC of allergic patients was inhibited by anti-TARC (CCL17) and anti-MDC (CCL22) neutralizing Abs. By using anti-IP10 (CXCL10) blocking Abs, supernatants of Der p 1-pulsed DC from healthy donors were shown to be involved in the recruitment of Th1 cells. These results suggest that in allergic patients exposed to house dust mites, DC may favour the exacerbation of the Th2 response via the increase in type 2 chemokine production.
Eur Cytokine Netw
PMID:Monocyte-derived dendritic cells exposed to Der p 1 allergen enhance the recruitment of Th2 cells: major involvement of the chemokines TARC/CCL17 and MDC/CCL22. 1471 13

The expression of chemokines has been suggested to involve an interdependent network, with the absence of a single chemokine affecting the expression of multiple other chemokines. Monocyte chemoattractant protein (MCP-1), a member of C-C chemokine superfamily, plays a critical role in the recruitment and activation of leukocytes during acute inflammation. To examine the effect of the loss of MCP-1 on expression of the chemokine network, we compared the mRNA expression profiles of MCP-1(-/-) and wild type mice during the acute inflammatory phase of excisional wounds. Utilizing a mouse cDNA array containing 514 chemokine and chemokine related genes, the loss of MCP-1 was observed to cause a significant upregulation of nine genes (Decorin, Persephin, IL-1beta, MIP-2, MSP, IL1ra, CCR5, CCR3, IL-11) and significant downregulation of two genes (CCR4 and CD3Z) in acute wounds. The array data was confirmed by semi-quantitative RT-PCR. The effect of MCP-1 deletion on chemokine expression was further examined in isolated macrophages. Compared to wild type, LPS-stimulated peritoneal macrophages from MCP-1(-/-) mice showed a significant increase in the expression of RANTES, MIP-1beta, MIP-1alpha and MIP-2 mRNA. The data suggest that loss of a single chemokine perturbs the chemokine network not only in the setting of acute inflammation but even in an isolated inflammatory cell, the macrophage.
Cytokine 2005 Apr 21
PMID:The effect of MCP-1 depletion on chemokine and chemokine-related gene expression: evidence for a complex network in acute inflammation. 1580 97


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