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)

The local cytokine response to uropathogenic phenotype Escherichia coli KBC211 infection exhibits characteristics of both TH1 and TH2 profiles. Interleukin (IL)-6, MIP-2, IL-12, IL-18, and tumor necrosis factor-alpha (TNF-alpha) are expressed, but IL-4, IL-5, and IL-10 are also present at low levels. This is clearly a complex response that should be explored more fully. The relative contributions of the bladder epithelium and other cells of the bladder wall should also be determined. Epithelial cytokine responses may be considerable, and because these cells are the first to encounter the pathogen, they will be of great importance in the immune response to pathogenic E. coli.
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PMID:Cytokine induction in murine bladder tissue by type 1 fimbriated Escherichia coli. 1209 61

We investigated the expression of Th1- and Th2-associated chemokine receptors on peripheral blood lymphocytes at diagnosis and in the first phase of type 1 diabetes. Peripheral blood mononuclear cells (PBMCs) of 25 patients with newly diagnosed type 1 diabetes, 10 patients with longstanding type 1 diabetes, and 35 healthy control subjects were examined for expression of the chemokine receptors CXCR4 (naive T-cells), CCR5 and CXCR3 (Th1 associated), and CCR3 and CCR4 (Th2 associated) on CD3+ lymphocytes. Furthermore, we analyzed chemokine serum levels (monocyte chemoattractant protein [MCP]-1, macrophage inflammatory protein [MIP]-1alpha, MIP-1beta, and RANTES [regulated on activation, normal T-cell expressed and secreted]) and phytohemagglutinin (PHA)-stimulated cytokine secretion of Th1- (gamma-interferon [IFN-gamma] and tumor necrosis factor-alpha [TNF-alpha]) and Th2 (interleukin [IL]-4 and -10)-associated cytokines by PBMC. The patients with newly diagnosed type 1 diabetes were followed for these parameters at 6-12 months after diagnosis. The PBMCs of patients with newly diagnosed but not with longstanding type 1 diabetes showed reduced expression of the Th1-associated chemokine receptors CCR5 (P < 0.001 vs. control subjects) and CXCR3 (P < 0.002 vs. control subjects). This reduction correlated with reduced IFN-gamma and TNF-alpha production of PBMCs after PHA stimulation and reversed 6-12 months after diagnosis to normal levels. CCR4 cells were reduced in both newly diagnosed and longstanding type 1 diabetic patients, which correlated to reduced PHA-stimulated IL-4 production. MIP-1alpha and MIP-1beta levels were considerably elevated in a subgroup of patients with newly diagnosed diabetes. We assume that Th1-associated peripheral T-cells are reduced in a narrow time window at the time of diagnosis of diabetes, possibly due to extravasation in the inflamed pancreas. Thus, chemokine receptor expression of peripheral blood lymphocytes may be a useful surrogate marker for the immune activity of type 1 diabetes (e.g., in intervention trials).
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PMID:Reduced expression of Th1-associated chemokine receptors on peripheral blood lymphocytes at diagnosis of type 1 diabetes. 1214 60

Results from previous studies indicate that hyperthyroidism increases the risk of ozone-induced lung toxicity. To better understand the processes that might contribute to the increased pulmonary inflammatory response to ozone in hyperthyroidism, we evaluated bronchoalveolar lavage fluid levels of selected cytokines in control and hyperthyroid rats after exposure to air or ozone. In addition, we assessed whether there is a relative increase in nuclear factor-kappa B (NF-kappaB) binding activity in cells harvested by bronchoalveolar lavage from hyperthyroid rats following the inhalation of ozone. A hyperthyroid condition was induced by the administration of thyroxine (0.5 mg/kg body weight) for 7 days. Control rats received vehicle injections. The animals were then exposed by inhalation to air or ozone (2 ppm for 3 h) and studied 18 h following the exposure. Bronchoalveolar lavage levels of MIP-2 and MCP-1 were increased in both control and hyperthyroid rats by ozone exposure. However, the increases in hyperthyroid rats were much greater, MIP-2 1.5-fold and MCP-1 11-fold, when compared to levels in controls following ozone. These changes appeared to be relatively specific; bronchoalveolar lavage fluid levels of interleukin (IL)-6, IL-4, and IL-10 were generally low or nondetectable across all of the studied groups at the 18-h postexposure time point. We also found that NF-kappaB binding activity was increased at both 4 and 18 h following ozone exposure in bronchoalveolar lavage cell extracts from hyperthyroid rats relative to the activity in control samples. Collectively, these results suggest that mechanisms contributing to the enhanced pulmonary inflammatory response to ozone in a hyperthyroid state include an increase in NF-kappaB activation and an upregulation of chemokine production.
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PMID:Influence of hyperthyroidism on rat lung cytokine production and nuclear factor-kappaB activation following ozone exposure. 1245 97

Previous studies with mice have shown that major histocompatibility complex class II (MHC-II) is required for protection from Helicobacter pylori, while MHC-I and antibodies are not. Thus, CD4(+) T cells are presumed to play an essential role in protective immunity via secretion of cytokines. To determine which cytokines are associated with a reduction of bacterial load in immunized mice, gastric cytokine expression was examined by semiquantitative reverse transcription-PCR in protected (defined as > or =2-log-unit decrease in bacterial load) and unprotected mice 4 weeks after challenge. Elevated levels of mRNA for interleukin-12p40 (IL-12p40), gamma interferon (IFN-gamma), tumor necrosis factor alpha, and inducible nitric oxide synthase (iNOS) were associated with protection in immunized-challenged (I/C) mice, but Th2 cytokine (IL-4, IL-5, IL-10, and IL-13) and chemokine (KC, MIP-2, and MCP-1) expression was not associated with protection. Despite the association of IFN-gamma and iNOS message with protection, I/C mice genetically lacking either of these products were able to reduce the bacterial load as well as the wild-type I/C controls. The I/C mice lacking IL-12p40 were not protected compared to unimmunized-challenged mice. All I/C groups developed gastritis. We conclude that neither IFN-gamma nor iNOS is essential for vaccine-induced protection from H. pylori infection. The p40 subunit of IL-12, which is a component of both IL-12 and IL-23, is necessary for protection in immunized mice. These findings suggest a novel IFN-gamma-independent function of IL-12p40 in effective mucosal immunization against H. pylori.
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PMID:Vaccine-induced reduction of Helicobacter pylori colonization in mice is interleukin-12 dependent but gamma interferon and inducible nitric oxide synthase independent. 1254 May 73

The initiation and maintenance of airway immune responses in Th2 type allergic diseases such as asthma are dependent on the specific activation of local airway dendritic cells (DCs). The cytokine microenvironment, produced by local cells, influences the recruitment of specific subsets of immature DCs and their subsequent maturation. In the airway, DCs reside in close proximity to airway epithelial cells (AECs). We examined the ability of primary culture human bronchial epithelial cells (HBECs) to synthesize and secrete the recently described CC-chemokine, MIP-3alpha/CCL20. MIP-3alpha/CCL20 is the unique chemokine ligand for CCR6, a receptor with a restricted distribution. MIP-3alpha/CCL20 induces selective migration of DCs because CCR6 is expressed on some immature DCs but not on CD14+ DC precursors or mature DCs. HBECs were stimulated with pro-inflammatory cytokines tumor necrosis factor-alpha and interleukin (IL)-1beta or, because of their critical role in allergic diseases, IL-4 and IL-13. Cells were also exposed to small size-fractions of ambient particulate matter. Each of these stimuli induced MIP-3alpha/CCL20 gene and protein expression. Moreover, these agents upregulated mitogen-activated protein kinase pathways in HBECs. Inhibition of the ERK1/2 pathway or p38 reduced cytokine-induced MIP-3alpha/CCL20 expression. These data suggest a mechanism by which AEC may facilitate recruitment of DC subsets to the airway.
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PMID:Airway epithelial cells release MIP-3alpha/CCL20 in response to cytokines and ambient particulate matter. 1276 Sep 62

Infection of mice with Leishmania major results in disease progression or resolution, largely depending on the genetic backgrounds of the mouse strains. Infection with Leishmania amazonensis, on the other hand, causes progressive cutaneous lesions in most inbred strains of mice. We hypothesized that deficient activation of early immune responses contributes to the pathogenesis in L. amazonensis-infected mice. To distinguish early molecular events that determine the outcome of Leishmania infections, we examined cytokine gene expression in C57BL/6 mice infected with either L. amazonensis or L. major (a healing model). After 2 to 4 weeks, L. amazonensis-infected mice had significantly delayed and depressed expression of inflammatory cytokines (interleukin-12 [IL-12], gamma interferon, IL-1 alpha, IL-1 beta), CC chemokines (CC chemokine ligand 3 [CCL3]/macrophage inflammatory protein 1 alpha [MIP-1 alpha], CCL4/MIP-1 beta, CCL5/RANTES, MIP-2), and chemokine receptors (CCR1, CCR2, CCR5) in foot tissues and draining lymph nodes compared to the expression in L. major-infected controls. These findings correlated with defective T-cell responsiveness to parasite stimulation in vivo and in vitro. Adoptive transfer of L. amazonensis-specific Th1 cells prior to infection overcame the immune defects of the animals, leading to complete control of the disease. Studies with gene knockout mice suggested that IL-10, but not IL-4, contributed partially to compromised immunity in L. amazonensis-infected hosts. The data suggest that there is impairment in multiple immune functions at early stages of infection with L. amazonensis parasites and provide a compelling rationale to explore immune augmentation as an intervention in American cutaneous leishmaniasis.
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PMID:Impaired expression of inflammatory cytokines and chemokines at early stages of infection with Leishmania amazonensis. 1287 3

Cytokines play a central role in the pathogenesis of allergic diseases and allergic inflammation. Therefore, an understanding of mechanisms which regulate production and function of cytokines is very important and may result in the development of more effective methods of treatment of allergic diseases. Recent studies have demonstrated that the induction of allergic inflammation requires genetic background and environmentak factors. The most important cytokines and chemokines are IL-4, IL-5, IL-3, IL-13, GM-CSF and TNF-alpha. Many other cytokines are responsible for the growth, maturity, migration activation and apoptosis of all cells involved in allergic inflammation, among them are IL-2, IL-5, IL-6, IL-9, MIP-1 alpha, RANTES, IL-8, IL-12, IL-18, IFN-alpha i gamma, TGF-beta, sIL-4, IL-1Ra. Recently it has been proven that IL-10 and other cytokines from the IL-10 family, and TGF-beta have anti-inflammatory properties in allergy.
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PMID:[Cytokines in allergic inflammation]. 1452 54

We have characterized leukocyte migration to the pleural cavity in a methylated-BSA (mBSA)-induced model of murine delayed-type hypersensitivity and evaluated the ability of IL-4 and IL-10 to modulate this response. Neutrophils, macrophages, T cells, and dendritic cells migrated to the pleural cavity in a time-dependent fashion following direct intrapleural antigen challenge, with neutrophils comprising the majority of exudate leukocytes in the cavity within the first 24 h and the number of mononuclear cells increasing at later times. Real-time quantitative PCR analysis of infiltrating leukocytes revealed a marked elevation of steady-state mRNA levels of IL-1beta and TNFalpha and the chemokines KC, MIP-2, CXCL9, CXCL10, CXCL11, CCL2, CCL3, and CCL4 at 6 h postchallenge, which diminished over time. In contrast, gammaIFN mRNA levels were maximal at 24 h and CCL5 expression was sustained throughout 72 h. ELISA analysis of pleural exudate fluid revealed significant elevations of KC and CCL2 protein levels at 6 h postantigen challenge and a peak increase in gammaIFN protein at 24 h, confirming our mRNA observations. Administration of recombinant murine IL-4 or IL-10 prior to challenge significantly blocked cell trafficking to the pleural cavity as well as peak levels of exudate gammaIFN, with IL-4 being more potent in impairing these responses. IL-4 administration also increased the proportion of naive T cells in the pleural cavity, as judged by CD62L and CD45RB expression. These results indicate that this in vivo model demonstrates a pattern of events associated with Th1-mediated leukocyte trafficking and underscore the potential utility of this in vivo model for evaluating therapeutic inhibitors of leukocyte trafficking.
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PMID:Impairment of leukocyte trafficking in a murine pleuritis model by IL-4 and IL-10. 1452 70

Human neonates are immunologically immature and consequently are highly susceptible to infection. The cellular basis for the dysfunctional immune responses of neonates is not clear, but is likely to reflect the immaturity of both B and T cell populations. Here we have examined the ability of human cord blood B cells to respond to antigen receptor cross-linking and also to CpG containing oligodeoxynucleotides (ODN), and compared their responses with those of adult peripheral blood B cells. Antigen receptor cross-linking with soluble F(ab')2 anti-IgM antibodies, induced HLA-DR and CD86 up-regulation and proliferation to a similar extent in adult and cord blood B cells. Both interleukin (IL)-2 and IL-4 co-stimulated anti-IgM-induced proliferation, but cord blood B cells were less sensitive than adult B cells to the co-stimulatory effects of IL-2. Antigen receptor cross-linking induced secretion of the chemokines macrophage inflammatory protein-1 alpha (MIP-1 alpha) and MIP-1 beta in adult and cord blood B cells, and secretion was enhanced by IL-2 or IL-4. CpG-ODN induced up-regulation of HLA-DR and CD86 expression and proliferation of adult and cord blood B cells, and anti-IgM and CPG-ODN synergized in the induction of proliferation. CpG-ODN also induced MIP-1 alpha and MIP-1 alpha secretion in adult and cord blood B cells. In addition to functional studies we examined the expression of CD62L (l-selectin), CCR7 and CXCR5. Our data show that surface expression of CD62L and CCR7 is lower on cord blood B cells than on adult B cells, suggesting that human cord blood B cells may exhibit homing defects.
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PMID:Functional responses of human neonatal B lymphocytes to antigen receptor cross-linking and CpG DNA. 1463 45

Antigen-stimulated naive CD4 T cells may differentiate into effector T cells such as Th1 and Th2 cells, or may remain as proliferating but uncommitted, primed, precursor cells (Thpp cells) that can subsequently differentiate into Th1 or Th2 cells in appropriate cytokine environments. To examine potential Thpp effector functions, we compared the genes expressed by mouse Thpp, naive, Th1 and Th2 cells, using Affymetrix GeneChip and RNase Protection assays. Similar to naive CD4 T cells, Thpp cells expressed IL-2 but not the cytokines characteristic of differentiated Th1 or Th2 cells, such as IFN-gamma, IL-4, or IL-5. However, Thpp, Th1 and Th2 cells, but not naive cells, expressed several CC chemokines including CCL1/TCA3, CCL5/RANTES, CCL3/MIP-1 alpha, CCL4/MIP-1 beta, and CCL9/MIP-1 gamma. Secretion of the corresponding proteins was confirmed by ELISA and Elispot. Consistent with this chemokine expression, supernatants of activated Thpp, Th1 and Th2 cells but not naive CD4T cells induced pertussis toxin-sensitive chemotaxis of B and T cells. Supernatants of Thpp cells did not bias differentiation of naive CD4 T cells towards either Th1 or Th2 cells. The secretion of several chemokines, but few cytokines, by primed uncommitted Thpp cells suggests that their activation during an immune response may recruit effector cells without directly polarizing effector functions.
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PMID:Synthesis of several chemokines but few cytokines by primed uncommitted precursor CD4 T cells suggests that these cells recruit other immune cells without exerting direct effector functions. 1516 31


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