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 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.
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PMID:Differential expression of cytokine genes in HIV-1 tat transfected T and B cell lines. 769 26

Macrophages, within the cytokine network, are a major source of many cytokines involved in immune response, hematopoiesis, inflammation and many other homeostatic processes. Upon stimulation by micro-organisms, microbial products or endogenous factors including cytokines, macrophages can de novo synthesize and release a large variety of cytokines (ie IL-1, IL-1ra, IL-6, IL-8, IL-10, IL-12, TNF alpha, IFN alpha, IFN gamma, MCP-1, MCP-3, MIF, M-CSF, G-CSF, GM-CSF, MIP-1, MIP-2, LIF, OSM, TGF beta). Some cytokines can upregulate the production of cytokines by macrophages (IL-3, GM-CSF, IFN gamma) while others can inhibit it (IL-4, IL-10, IL-13, TGF beta). In addition, these cytokines can modulate most of the macrophage functions and cell surface marker expression. Other cytokines (the chemokines such as MCP-1,2,3, MIP-1,2 and RANTES) contribute to the recruitment of circulating monocytes within tissues. It is worth noting that macrophages can be their own source of regulatory cytokines.
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PMID:Cytokines and macrophages. 785 54

To date no hematopoietic progenitors of dendritic Langerhans' cells (DLC), which represent an highly efficient class of antigen presenting cells, have been identified or the cytokines they elaborate have been defined. Here we describe an acute leukemia patient whose blasts (90-96% in peripheral blood and bone marrow) had a phenotype consistent with putative progenitors of DLC. The patient was treated with ara-C and VP-16 but did not achieve remission. The blasts had lobulated nuclei, no cytoplasmic vacuolation or Auer rods and were weakly positive for acid phosphatase and non-specific esterase and negative for PAS, granzyme A, dipeptidyl aminopeptidase IV, ATPase/ADPase and lysozyme production. The blasts were positive for CD1a, CD4, CD16, CD35, HLADR, HLADQ, CD11b, CD11c, CD14, CD33, CD34, CD11a, CD71, CD19, CD25, IL-2R beta and negative for CD2, CD7, CD8, CD10, CD22, CD56, CD57, surface or cytoplasmic CD3, TCR delta and TCR beta, HTLV-1p19 and P-glycoprotein. On liquid culture with or without 5 x 10(-9) M 12-O-tetradecanoylphorbol-13-acetate (TPA) for 3 days, the blasts formed aggregates of proliferating and elongating cells on the wall of the flasks with a decline in CD34, numerous dendritic processes appeared on the cells and there was strong positivity for ATPase/ADPase, but no other changes in phenotype. No macrophages were observed, indicating derivation from separate DLCs. Cytogenetic analysis showed chromosomal abnormalities and electron microscopy showed Birbeck granules. Southern blotting of DNA showed rearrangement of one allele for both JH and TCR beta but no HTLV-1 related sequences. Culture supernatants from blasts cultured with or without TPA showed the production of large amounts of IL-8, IL-6, TNF-alpha, MIP-1 alpha, IL-10 and interferon gamma and modest amounts of IL-1 alpha, GM-CSF and stem cell factor. The presence not only of CD1a, HLADR, HLADQ and many other characteristics including Birbeck granules, but also differentiation along the lines of DLC with appearance of dendritic processes on the cells and expression of ATPase/ADPase activity, indicate that the leukemic blasts in our patient represented a leukemic counterpart of normal progenitors of DLC and the leukemia a new entity which could possibly be classified as AML-M8. Lastly, many pro-inflammatory cytokines produced by DLC could contribute to inflammation and IL-10 to immunosuppression.
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PMID:Phenotype, genotype and cytokine production in acute leukemia involving progenitors of dendritic Langerhans' cells. 791 55

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)
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PMID:Interleukin-5 receptor alpha chain mRNA is down-regulated by transforming growth factor beta 1. 804 55

Peritoneal injection of thioglycollate medium (TM) to mice results in a dramatic increase in total number of peritoneal macrophages within 48 to 72 hours. Unlike resident macrophages, a fraction (10 to 20%) of these newly arrived young macrophages, designated as macrophage colony-forming cells (M-CFC), are highly proliferative and formed macrophage colonies in vitro in the presence of either macrophage or granulocyte-macrophage colony-stimulating factor (M-CSF or GM-CSF). Using a reverse transcriptase polymerase chain reaction (RT-PCR) technique, peritoneal exudate macrophages (PEM) obtained 2 to 5 days after a single TM injection actively expressed mRNA for recombinant murine macrophage inflammatory protein-1 alpha (rmMIP-1 alpha). Yet none or only a trace amount of mRNA for MIP-1 alpha was detected in normal resident macrophages or PEM obtained 7 days after TM treatment. The effect of rmMIP-1 alpha on the induction of exudate M-CFC was investigated. Multiple intraperitoneal (IP) administration of rmMIP-1 alpha caused a marked increase in the total number of peritoneal M-CFC and macrophages similar to but weaker than the increase in TM-injected mice. The total number of neutrophils, mast cells, and eosinophils also increased, but with different kinetics, following multiple injections of rmMIP-1 alpha. rmMIP-1 alpha alone did not stimulate the proliferation of M-CFC, nor did it potentiate their responsiveness to either rmGM-CSF or recombinant human (rh) M-CSF in vitro. Taken together, our results suggest that MIP-1 alpha released by exudate macrophages is a major chemoattractant responsible for the migration of M-CFC from the circulation to the peritoneal cavity during a TM-induced inflammatory response.
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PMID:Induction of murine peritoneal macrophage colony-forming cells by peritoneal administration of macrophage inflammatory protein-1 alpha. 840 40

We present a detailed analysis of cytokine expression patterns of the two permanent human bone marrow stromal cell lines, L87/4 and L88/5. These cell lines, previously established in our laboratory, are highly radiotolerant without cell detachment and support long-term cultures of CD(34+)-enriched human cord blood cells. RT-PCR analysis of 22 different cytokines or cytokine receptor mRNAs showed an almost identical expression pattern in the two stromal cell lines compared to primary human Dexter-type stroma. Since stromal feeder lines employed in long-term cultures usually are irradiated and grown in media containing corticosteroids, we analyzed the impact of irradiation and dexamethasone on cytokine production in the two cell lines by RT-PCR, Northern blot analysis, bioassays, and RIAs. By RT-PCR analysis, constitutive mRNA expression of c-kit, G-CSF, GM-CSF, IL-1 beta, IL-6, IL-7, IL-8, IL-11, Kit ligand (KL), LIF, M-CSF, MIP-1 alpha, TGF-beta, and TNF-alpha was demonstrated in both cell lines, with L87/4 a more potent cytokine producer than L88/5. Northern blot data showed an increase in mRNA levels for GM-CSF, IL-1 beta, and LIF by irradiation and IL-1 alpha treatment in both cell lines. IL-1 alpha-induced GM-CSF, IL-1 beta, IL-6, IL-11, and LIF mRNA levels were reduced by the addition of dexamethasone, whereas dexamethasone had no influence on the amounts of IL-1 alpha-induced G-CSF mRNA. L87/4 and, to a lower extent, L88/5 cells showed dexamethasone-dependent increases in KL mRNA, while KL mRNA levels were not stimulated by IL-1 alpha.
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PMID:Constitutive and modulated cytokine expression in two permanent human bone marrow stromal cell lines. 853 85

The aim of this study was to measure the level of cytokines produced by peripheral blood mononuclear cells (PBMNC) in patients with aplastic anemia (AA) and determine their effect on normal bone marrow (BM) colony growth. Thirty-five patients with AA and 21 normal controls were enrolled in the study. Medium conditioned by PBMNC of AA patients in the presence of phytohemagglutinin (PHA) was found to be suppressive to the clonal growth of normal BM cells. Thus, we further determined the presence in the PBMNC conditioned medium (CM) of inhibitory cytokines (macrophage inflammatory protein-1 alpha [MIP-1 alpha], transforming growth factor-beta 2 [TGF-beta 2], interferon-gamma [IFN-gamma], and tumor necrosis factor-alpha [TNF-alpha]) and stimulatory cytokines (granulocyte-macrophage colony-stimulatory factor [GM-CSF], interleukin-3 [IL-3], and stem cell factor [SCF]). The results show no significant difference between AA patients and normal controls in the spontaneous production of all cytokines by PBMNC. After PHA stimulation, the production of MIP-1 alpha, IFN-gamma, TNF-alpha, and GM-CSF significantly increased in the cultures of AA patients (p = 0.0009, 0.0002, 0.0022, and 0.0156, respectively). However, both TGF-beta 2 and SCF were undetectable in most of the tested samples. IL-3 was measured in the conditioned medium only after PHA stimulation, but without significant difference between the two groups (p = 0.67). Furthermore, the myelopoietic suppressing effect of AA-PBMNC CM could be significantly blocked by pretreatment with specific antibodies to the corresponding inhibitory cytokines (MIP-1 alpha, IFN-gamma, and TNF-alpha). After antibody neutralization, an apparent change occurred in the clonal growth of normal BM cells incubated with AA-PBMNC CM, resulting in colony enhancement of 205, 131, and 237% by anti-MIP-1 alpha, anti-IFN-gamma, and anti-TNF-alpha, respectively. These results suggest that overproduction of inhibitory cytokines, rather than underproduction of stimulating cytokines, may play a role in the progression of at least some patients with AA.
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PMID:Production of hematopoietic regulatory cytokines by peripheral blood mononuclear cells in patients with aplastic anemia. 853 89

The mRNA expression for 21 kinds of cytokines was measured in six human esophageal cancer cell lines using RT-PCR. More than moderate levels of RNA for IL-1 alpha were expressed in six of six cell lines, IL-1 beta in four, IL-6 in six, IL-7 in five, IL-10 in six, G-CSF in six, GM-CSF in six, SCF in six, MIP-2 beta in two, and LIF in six. None of the tumors expressed detectable message for IL-2, 3, 4, 5, 8, 11, 13, or IRAP after 30 cycles of PCR amplification. IL-1 alpha, IL-6, M-CSF, and GM-CSF levels in the culture supernatants were detectable using ELISA in three of six, four of six, one of six, and six of six ECCs, respectively. IL-1 beta, IL-2, TNF-alpha, and G-CSF were not detectable in all ECCs. There was no correlation between cytokine mRNA expression and production. These results suggest the existence of a complicated cytokine network around esophageal carcinomas that may affect their growth and proliferation.
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PMID:Cytokine mRNA expression patterns in human esophageal cancer cell lines. 859 Mar 2

Macrophage-stimulating protein (MSP), originally identified as an inducer of murine resident macrophage responsiveness to chemoattractants, is a ligand for human RON/murine STK receptor protein tyrosine kinases. Since STK was cloned from populations enriched for hematopoietic stem cells, we initiated studies on the effects of MSP on colony formation by granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and multipotential (CFU-GEMM) myeloid progenitor cells. MSP alone had no colony stimulating activity. However, MSP caused about a 50% suppression of CFU-GM colony formation induced by synergistic combinations of SLF or Flt-L plus GM-CSF, G-CSF, or IL-3 and of BFU-E and CFU-GEMM colonies induced by SLF or Flt3-L plus Epo or Epo and IL-3. In contrast, MSP had no effect on progenitors stimulated by one growth factor. MSP also suppressed colony formation by stimulated cord blood progenitors, but only after preinduction to a rapidly cycling state. It was previously reported that several members of the chemokine family synergistically suppress myeloid progenitor proliferation. Likewise, synergistic suppression was observed when MSP was paired with VEGF, MIP-1 alpha, IL-8, PF4, MCP-1, IP-10, or ENA-78, or when VEGF was paired with the chemokines; and the required MSP concentration was more than 100-fold less than for MSP alone. Additionally, MSP or VEGF inhibited proliferation of the human myeloid growth factor-dependent cell line, M07e, but a sustained effect required multiple additions over time. At the least, some of the MSP suppressive effects on myeloid progenitors, as assessed on single isolated CD34 marrow cells, appeared to be directly on the progenitors; sustained additions of MSP were required to see this effect. The suppressive action of MSP and its synergism with proteins of the chemokine family may be of relevance to regulation of blood cell production.
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PMID:Macrophage-stimulating protein, a ligand for the RON receptor protein tyrosine kinase, suppresses myeloid progenitor cell proliferation and synergizes with vascular endothelial cell growth factor and members of the chemokine family. 869 17

We defined a cytokine mRNA profile of 12 ovarian cancer biopsies, 10 normal/benign biopsies, six ovarian cancer cell lines and three ovarian cancer xenografts, using RT-PCR. The profile, based on screening for 25 cytokines and 12 receptor mRNAs, was rich in growth factors, pro-inflammatory cytokines and chemokines, but weak in lymphocyte-associated cytokines. The pattern was unique to ovarian tissue, but similar in normal, benign and malignant biopsies, with > 80% samples expressing 16 cytokines in common. Fourteen of these were also expressed by > 65% cell lines, but fewer were detected in xenografts. Potential autocrine loops existed for IL-1, IGF-1, M-CSF, GM-CSF and TNF-alpha. IL-4 and IFN-gamma receptors were expressed in absence of ligand. Chemokines RANTES, MIP-1 alpha and MIP-1 beta were expressed in biopsies, but were rarely detected in cell lines and absent from xenografts. IGF-1 and its receptor was expressed in every sample, as was IFN-gamma receptor. Another 10 cytokine mRNAs and six receptors were expressed in > 80% samples. These may contribute to key survival/growth loops. Similarities between normal and malignant biopsies suggest that analogous processes of remodelling and repair occur. RT-PCR proved a rapid, reproducible screen, but further assays are required to detect quantitative differences between normal and malignant tissues and tumour models.
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PMID:A cytokine profile of normal and malignant ovary. 889 39


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