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

The murine macrophage inflammatory proteins-1 alpha (MIP-1 alpha) and MIP-1 beta are distinct but closely related cytokines. Partially purified mixtures of the two proteins affect neutrophil function and cause local inflammation and fever. The particular properties of MIP-1 alpha have not been well studied, although it has been identified as being identical to an inhibitor of haemopoietic stem cell growth. We have expressed MIP-1 alpha in yeast cells and purified it to sequence homogeneity. Structural analysis of this biologically active material by circular dichroism and fluorescence spectroscopy confirms that MIP-1 alpha has a very similar secondary and tertiary structure to platelet factor 4 and interleukin 8 with which it shares limited sequence homology. The in-vitro stem cell inhibitory properties have been confirmed using a range of murine progenitor cells including purified bone marrow progenitor cells (FACS-1), the FDCP-mix A4 cell line, and spleen colony forming unit (CFU-S) populations. Plateau levels of inhibition of stem cell growth were achieved using concentrations of 0.15 micrograms/ml MIP-1 alpha. We have also demonstrated that MIP-1 alpha is active in vivo: 5 micrograms of MIP-1 alpha per mouse given as a bolus injection, protects stem cells from subsequent in-vitro killing by tritiated thymidine. MIP-1 alpha was also shown to enhance the proliferation of more committed progenitor granulocyte macrophage-colony forming cells (GM-CFC) in response to granulocyte macrophage-colony stimulating factor (GM-CSF).
Cytokine 1992 Jan
PMID:Biological and structural properties of MIP-1 alpha expressed in yeast. 161 59

Macrophages are essential for normal wound repair and many of their effects on healing wounds are likely to be mediated by the secretion of cytokines. This study examines the appearance of messenger RNA (mRNA) for cachectin/tumor necrosis factor (TNF), IL 1, and macrophage inflammatory proteins 1 and 2 (MIP-1 and MIP-2), as well as the mature peptides, in a model of wound healing using wound chambers. RNA for all four cytokines can be detected in wound inflammatory cells by polymerase chain reaction amplification throughout the first 7 days. Cachectin/TNF and IL 1 protein levels peaked on the first day after wound chamber implantation, and MIP-1 and MIP-2 were detected only on day 3. The data suggest that these cytokines participate in the early inflammatory response to wounding.
Cytokine 1990 Mar
PMID:Cytokine production in a model of wound healing: the appearance of MIP-1, MIP-2, cachectin/TNF and IL-1. 210 19

The present report compares a variety of T cell purification protocols and chemotaxis procedures in assessing chemokine-induced T cell migration using a microchemotaxis assay. Rapidly purified T cells are capable of directly responding to the beta chemokines macrophage inflammatory protein-1 alpha (MIP-1 alpha), MIP-1 beta, and RANTES in the absence of alpha CD3 stimulation as previously described (Taub, D.D. and Oppenheim, J.J. (1993) Cytokine 5, 175). However, T cell purification schemes involving prolonged 37 degrees C incubations generally produce non-motile T lymphocytes that require stimulation with alpha CD3 antibody for 6-12 h in culture to recover chemotactic mobility. This loss of chemotactic potential appears to be due to prolonged 37 degrees C incubations as rapidly purified T cells lose migratory activity upon incubation at 37 degrees C. Radiolabeled binding analysis revealed that beta chemokine binding sites are downregulated as short as 2 h after incubation at 37 degrees C. T cells require the presence of extracellular matrix molecules to facilitate T cell migration. While many of these proteins permit chemotactic activity, human plasma and foreskin fibronectin were found to be the most effective matrix molecule for T cell migration. Kinetic analysis of T cell activation revealed that 6-12 h of anti-CD3 stimulation was optimal to restore the ability of purified T cells to migrate in response to the chemokines MIP-1 alpha, MIP-1 beta, RANTES, and IL-8. However, rapidly dividing T cells (> or = 48 h post alpha CD3 mAb stimulation) fail to migrate in response to any chemotactic stimulus. Together, these results suggest that the measurement of T cell migration, using microchemotaxis chambers, is a multifactorial process with strict environmental and activation requirements.
 ...
PMID:Chemotaxis of T lymphocytes on extracellular matrix proteins. Analysis of the in vitro method to quantitate chemotaxis of human T cells. 754 17

Dendritic cells are the most potent antigen-presenting cells of the immune system. Although dendritic cells are likely to secrete selective cytokines that facilitate antigen presentation, the difficulty in isolating pure dendritic cells in sufficient numbers has made assessment of this function imprecise. In this study, pure populations of CD83+ human blood dendritic cells were isolated by previously established enrichment procedures and subsequent cell sorting. Cytokine gene expression was assessed by reverse transcription-polymerase chain reaction (RT-PCR) amplification of mRNA. Resting CD83+ dendritic cells expressed interleukin-6 (IL-6), IL-8, IL-10, tumor necrosis factor-alpha (TNF-alpha), and transforming growth factor-beta 1 (TGF-beta 1) mRNA, while activation of cells with phorbol myristate acetate induced IL-1 alpha and beta, IL-9, TNF-beta, interferon-gamma, granulocyte-macrophage colony-stimulating factor (GM-CSF), M-CSF, and G-CSF mRNA expression. Resting CD83+ cells also expressed the Rantes, MCP-1, MIP-1 alpha, and MIP-1 beta chemokines, with 1-309 expression induced upon activation. Resting and activated CD83+ dendritic cells also expressed receptors for IL-2 (CD25), TGF-beta 1 and -beta 3, and GM-CSF as determined by indirect immunofluorescence staining. These results indicate that dendritic cells have the ability to produce a variety of soluble factors which are likely to contribute substantially to the potent allostimulatory activity of these cells.
 ...
PMID:A distinct pattern of cytokine gene expression by human CD83+ blood dendritic cells. 757 30

The in vitro mixed lymphocyte reaction (MLR) is regarded as a model of responsiveness to allogeneic major histocompatibility complex antigens and has historically been used to elucidate the pathway of T lymphocyte proliferation. In addition, the MLR response may reflect activation pathways relevant in acute allograft rejection. In the present study, we have applied the MLR to examine the role of adhesion molecules intercellular adhesion molecule-1 and lymphocyte function-associated antigen-3 in the induction of tumor necrosis factor-alpha (TNF-alpha) as well as chemotactic cytokines, interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1 alpha (MIP-1 alpha). Monoclonal antibodies to the adhesion molecules (5 micrograms/ml) were added to one-way human MLR cultures and supernatants collected at various time points. The monoclonal antibodies to the adhesion molecules significantly suppressed the proliferative response by 50 to 80%. Cytokine production, TNF-alpha (3.2 +/- 0.5 ng/ml), MIP-1 alpha (12.9 +/- 3.3 ng/ml), MCP-1 (18.8 +/- 3.4 ng/ml), and IL-8 (57 +/- 18 ng/ml) peaked on day 5 of the assay. The addition of anti-intercellular adhesion molecule-1 to the cultures suppressed TNF-alpha, MIP-1 alpha, MCP-1, and IL-8 production by 68% (1.05 +/- 0.29 ng/ml), 85% (2.0 +/- 1.2 ng/ml), 63% (6.8 +/- 2.9 ng/ml), and 47% (30.3 +/- 3.7 ng/ml), respectively. Likewise, the addition of anti-lymphocyte function-associated antigen-3 monoclonal antibody suppressed the cytokines by 78% (0.71 +/- 0.34 ng/ml), 66% (4.5 +/- 2.2 ng/ml), 52% (8.8 +/- 2.2 ng/ml), and 73% (15.7 +/- 4.4 ng/ml), respectively. Immunohistochemical staining indicated that monocytes were the primary source of the chemokines IL-8, MCP-1, and MIP-1 alpha. The addition of exogenous recombinant TNF-alpha (5 ng/ml) or recombinant IL-2 (5 units/ml) to the anti-intercellular adhesion molecule-1-treated cultures allowed the recovery of the proliferative response as well as restoration of IL-2, TNF-alpha, and IL-8, but not MCP-1 or MIP-1 alpha, indicating that both soluble and adhesion molecule signals are required for the production of the C-C family of chemokines in allogeneic responses. Thus, the events resulting in cellular proliferation and chemokine production were dependent on adhesion molecule interactions.
 ...
PMID:The production of chemotactic cytokines in an allogeneic response. The role of intercellular adhesion molecule-1 and lymphocyte function-associated antigen-3. 769 33

Cytokine responses are dramatically affected when HIV-1 infected cells are activated with certain antigenic stimuli. We report the effects of HIV-1 tat gene in cytokine modulation, using HIV-1 tat transfected T (Jurkat) and B (Raji) cell lines. Studying the effect of tat and/or PMA + PHA on mRNA expression of 14 cytokines (IL-1 alpha, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, TNF-alpha, TNF-beta, GM-CSF, TGF-beta, IFN-gamma and MIP-1 alpha) illustrated differential effects. In addition to the varied effects of tat on the steady state levels of cytokine mRNAs, tat induced the secretion of TNF-beta preferentially in both B and T cell lines, either by itself as in Raji B cell line or synergistically upon PMA + PHA stimulation as in Jurkat T cell line.
 ...
PMID:Differential expression of cytokine genes in HIV-1 tat transfected T and B cell lines. 769 26

Cytokine production in macrophages infected by bacteria is critical for the course of infection. However, it is not known how infection of macrophages with opportunistic bacteria leads to cytokine production in different populations of cells. Since it is possible that cytokine genes may be differentially regulated by attachment rather than by active infection, the levels of various cytokine mRNAs were measured in alveolar macrophages (AMs), peritoneal resident macrophages (RMs), and peritoneally elicited macrophages (EMs) interacting with Legionella pneumophila by using cytochalasin D-treated macrophages and a newly developed quantitative reverse transcription-PCR procedure with high-performance liquid chromatographic analysis to determine cytokine mRNA formation. Increased levels of interleukin-1 beta (IL-1 beta), IL-6, tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor, and macrophage inflammatory protein 2 mRNAs were quantitated in the macrophages responding to L. pneumophila attachment in vitro. Using this technique, we showed that the three different macrophage populations responded differently to bacterial attachment. We found that the levels of IL-6 and granulocyte-macrophage colony-stimulating factor mRNAs induced by the attachment of L. pneumophila to AMs were significantly lower than the levels in RMs but similar to the levels in EMs. Furthermore, the levels of MIP-2 mRNA in the AMs were found to be higher than those in the RMs, but similar levels were found in EMs. IL-1 beta mRNA levels were higher in both AMs and RMs than in EMs, but tumor necrosis factor alpha levels were not different among the three macrophage populations examined. Thus, the responses of macrophages to bacterial attachment in terms of cytokine mRNA levels were readily quantitated by the reverse transcription-PCR assay. However, the results obtained showed different levels of responsiveness of distinct macrophage populations to L. pneumophila attachment, and this could be related to the characteristic nature of the macrophage type examined.
 ...
PMID:Quantitative reverse transcription-PCR analysis of Legionella pneumophila-induced cytokine mRNA in different macrophage populations by high-performance liquid chromatography. 771 7

The Burkitt's lymphoma receptor 1 (BLR1) identified initially in Burkitt lymphoma cells has been the first member of the superfamily of G-protein-coupled receptors with a lymphocyte specific expression pattern. BLR1 shows significant relationship to receptors for chemokines (IL-8, MIP-1 beta) and neuropeptides. The gene encoding the murine homologue of the human BLR1 receptor was isolated and used to study its tissue-specific expression. Blr-1 consists of two exons encoding a protein of 374 amino acid residues which shows 83% identity with the human homologue. Screening of normal tissues of adult BALB/c mice revealed that blr-1-specific RNA is detected consistently at low levels in secondary lymphatic organs. The blr-1 gene is expressed regularly and strongly in lymphomas of mature B cells but not in plasmacytomas. SCID mice deficient in the development of mature B cells have strongly reduced levels of blr-1-specific RNA in the spleen. Cytokine mediated induction (IL4, IL6) of terminal differentiation of resting B cells towards Ig-secreting plasma cells completely downregulates expression of blr-1. RNA in situ hybridization using brain sections demonstrates blr 1 transcription in the granule and Purkinje cell layer of the cerebellum. The precise delineation of the restricted expression pattern of the blr-1 gene will support the identification of its ligand and may provide a clue to understand how BLR1 exerts its biological function within the immune and nervous system.
 ...
PMID:Selective expression of the murine homologue of the G-protein-coupled receptor BLR1 in B cell differentiation, B cell neoplasia and defined areas of the cerebellum. 792 Jan 82

Synovial pannus represents a hypertrophic and locally invasive connective tissue response to chronic inflammation that accounts in large part for the periarticular destruction of rheumatoid arthritis. Synovial fibroblasts cultured from rheumatoid synovia have been found to display an increased rate of proliferation and the constitutive expression of collagenases, growth factors, and inflammatory cytokines. The existence in rheumatoid synovium of both a pro-inflammatory state and growth dysregulation led us to investigate the expression by synovial fibroblasts of the closely homologous cytokines GRO alpha (gro/MGSA), GRO beta (MIP-2 alpha), and GRO gamma (MIP-2 beta). These cytokines are released by a variety of cell types and display overlapping growth regulatory and pro-inflammatory activities. In contrast to expectations, the majority of synovial fibroblast cell lines derived from osteoarthritic or non-inflammatory synovia showed a relative increase in the constitutive expression of GRO alpha and GRO beta when compared to synovial fibroblasts obtained from rheumatoid synovia. Considered together with evidence that GRO alpha is a growth regulator that modulates the expression of metalloproteinase activity, these findings provide evidence for a differential pathway of cytokine activation that may downregulate the proliferative and erosive response to chronic arthritis.
Cytokine 1994 Jan
PMID:Differential expression of the small inducible cytokines GRO alpha and GRO beta by synovial fibroblasts in chronic arthritis: possible role in growth regulation. 800 35

Interleukin-5 is a T cell-derived cytokine with actions restricted to the eosinophil/basophil lineage and a subset of murine B cells. High affinity receptors have been identified and shown to comprise an IL-5-specific alpha chain (IL-5R alpha) in association with a beta chain which is shared with the receptors for IL-3 and GM-CSF. Nothing is currently known of the factors which regulate the transcription and subsequent expression of the IL-5 receptor alpha chain; this study was undertaken, therefore, in order to identify agents which modulate IL-5R alpha mRNA levels, with the goal of understanding the regulation of this gene in vivo. The human IL-5-dependent erythroleukemia TF-1 was used as a source of mRNA which was analysed by northern blotting using a cDNA probe for IL-5R alpha. A range of cytokines and pharmacological agents were used in 20 hour cultures of TF-1 followed by northern analysis. Of these, only TGF-beta 1 and PMA showed any effect, which was a selective downregulation, although the PMA displayed some cytotoxicity over the long culture period. The remainder (interleukins 1 to 11, G-CSF, GM-CSF, LIF, SCF, erythropoetin, IFN-gamma, RANTES, MIP-1 alpha, FGF, EGF, PDGF, dexamethasone, forskolin, retinoic acid and cyclosporin A) failed to alter expression.(ABSTRACT TRUNCATED AT 250 WORDS)
Eur Cytokine Netw
PMID:Interleukin-5 receptor alpha chain mRNA is down-regulated by transforming growth factor beta 1. 804 55


1 2 3 4 5 6 7 8 9 10 Next >>