EC:3.4.24.59 - FACTA Search

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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 production of chemotactic cytokines (chemokines) and other cytokines by macrophages in response to fungal infection is thought to be critical during the course of candidiasis. However, the mechanism of cytokine synthesis by macrophages in response to fungi is not well understood. Therefore, the response of macrophages to Candida albicans was examined in terms of receptor-mediated chemokine and other cytokine mRNA induction. Attachment of C. albicans to murine thioglycollate-elicited peritoneal macrophages induced increased mRNA levels of the cytokines interleukin-1beta (IL-1beta), IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF) and the chemokines macrophage inflammatory protein 1beta (MIP-1beta), MIP-2, and KC (a member of the platelet factor 4 neutrophil chemoattractant family), as determined by quantitative reverse transcription-PCR. However, treatment of macrophages with alpha-methyl-D-mannoside significantly reduced the cytokine GM-CSF response to C. albicans but did not affect the chemokine MIP-2 response. Antisense oligodeoxynucleotide (ODN) to mannose receptor (MR) mRNA inhibited the expression and function of MR in macrophages as determined by Western blot analysis and 125I-labeled mannose-bovine serum albumin (BSA) binding, and also inhibited the elevation of cytokine IL-1beta, IL-6, and GM-CSF mRNA levels induced by C. albicans attachment. Elevation of chemokine MIP-1beta, MIP-2, and KC mRNA levels induced by C. albicans was not affected in macrophages whose MR expression was suppressed by antisense ODN treatment. Furthermore, IL-4 treatment of macrophages, which up-regulated MR expression as determined by Western blot analysis and fluorescein isothiocyanate-labeled mannose-BSA uptake, enhanced the level of cytokine GM-CSF mRNA induced by C. albicans but not the level of the chemokine MIP-2 mRNA. These results indicate that selected cytokine responses of macrophages to C. albicans are mediated by MR, while some chemokine responses may be mediated by other receptors.
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PMID:Involvement of mannose receptor in cytokine interleukin-1beta (IL-1beta), IL-6, and granulocyte-macrophage colony-stimulating factor responses, but not in chemokine macrophage inflammatory protein 1beta (MIP-1beta), MIP-2, and KC responses, caused by attachment of Candida albicans to macrophages. 903 18

The expression of cytokines can dictate the intensity, chronicity, and type of immune/inflammatory response that is produced. These events may be regulated by accumulation of particular cell populations at a site of immune response that can be regulated by the expression of specific chemokines. Recent data have indicated that chemokines also have direct effects on cellular activation. In particular, T lymphocyte responses have been divided into two distinct phenotypes, designated by TH1- and TH2-type cytokine expression. Although it is recognized that divergent T-lymphocyte-derived cytokine phenotypes exist, the mechanisms that dictate the expression of these cytokines and ultimately the division of these immune responses is not entirely clear. In the present study, we present data that the C-C chemokine family members may be a factor influencing the direction of T-cell-derived lymphokine production. To elucidate the role of C-C chemokines, MIP-1 alpha and MCP-1, we have used both antigen-specific (schistosomal egg antigen (SEA)) and nonspecific (conconavalin (Con) A) stimuli. Using TH2-type lymphocyte populations from SEA-sensitized mice, a significant increase in IL-4 mRNA expression and protein production was observed when MCP-1 was added to the culture. Conversely, MIP-1 alpha treatment appeared to decrease interleukin (IL)-4 production. Interestingly, the proliferative response in the TH2-type (SEA-specific) response was up-regulated by MIP-1 alpha whereas MCP-1 down-regulated the response, inversely correlating with IL-4 production. Primary stimulation of naive lymphocytes with Con A induces a predominant interferon (IFN)-gamma response, whereas the second stimulation of the same lymphocytes with Con A induces both IFN-gamma and IL-4. When the two C-C chemokines were individually co-incubated with Con-A-stimulated lymphocytes, both up-regulated IFN-gamma production and proliferation during the primary stimulation. Similarly, in the secondary response, both chemokines further upregulated IFN-gamma production; however, only MCP-1 co-stimulation increased IL-4 production, whereas MIP-1 alpha significantly decreased IL-4 production in these same cell populations. These results were also reflected in steady-state levels of mRNA expression. These results suggest that the production of C-C chemokines (MCP-1 or MIP-1 alpha) during an immune response may aid in determining the type of cytokines produced and the level of lymphocyte activation during a particular response.
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PMID:C-C chemokines differentially alter interleukin-4 production from lymphocytes. 913 8

Adult T cell leukemia (ATL) cells show a mature helper-inducer T cell phenotype and are thought to secrete many kinds of cytokines in vivo, complicating the clinical features in these patients. In an attempt to specify the cytokines produced by ATL cells, we measured the cytokine concentration in the culture supernatants of three ATL cell lines, all of which were confirmed to be true peripheral blood ATL cell in origin. All these cell lines showed the same cytokine production profile, secreting IL1-alpha, IL1-beta, LD78(MIP-l alpha), TNF-alpha, IFN-gamma, and GM-CSF, but not secreting IL-1 alpha, IL-1 beta, IL-1 receptor antagonist (IL-1 Ra), IL-4, IFN-alpha, and G-CSF irrespective of the stimulatory agents used. Such limited cytokine production may indicate the specific origin of ATL cells within the helper-inducer T cell subtypes. Moreover, these results explain some of the unusual clinical features of ATL patients.
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PMID:Features of the cytokines secreted by adult T cell leukemia (ATL) cells. 917 9

Cyclosporin A (CsA) is a potent immunosuppressant affecting many components of cellular and humoral immunity. Its main action probably results from inhibition of T-lymphocyte activation and interference with secretion of cytokines like IL-2, IL-4, IFN-gamma and TNF-alpha. Correspondingly, CsA has beneficial effects on the course of several autoimmune diseases thought to be mediated by T-lymphocytes, including a mild effect on multiple sclerosis. We exposed CD4 + cytotoxic T-lymphocytes specific for myelin basic protein, a putative target autoantigen in MS, to CsA in vitro, and determined the drug's effects on proliferation, expression of high affinity IL-2R, secretion of the proinflammatory cytokines IFN-gamma and TNF-alpha as well as on the secretion of the chemokines MIP-1 alpha and MIP-1 beta. In all instances, we observed a partial to complete inhibition. In contrast, the response of activated cells to IL-2 was resistant to CsA. Our observations are in line with results obtained in different experimental systems. The discrepancy between the profound inhibition of T-cells and the modest therapeutic effects on MS is discussed.
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PMID:In vitro modulation of human, autoreactive MBP-specific CD4 + T-cell clones by cyclosporin A. 918 37

We have successfully cloned nine NKR-P1+ TCR alpha beta + cells from PVG rat spleens, utilizing murine macrophage inflammatory protein-1 alpha (MIP-1 alpha) and IL-2. These clones are either double negative (DN, CD4-CD8-), which included clones 3.31, 3.71, 4.19, 4.59 and 4.65, or single positive (SP, CD4+CD8-), which included clones 1.64, 3.8, 3.76 and 3.78. No CD8+ clone was recovered. All nine clones are restricted in terms of their expression of the V beta antigens, since they express V beta 8.2 but not V beta 8.5, V beta 10 or V beta 16. These clones are agranular and they fall to generate NK or LAK activity upon incubation with IL-2, IL-12 or their combination. On the basis of their production of intracellular cytokines they can be divided into three categories: (I) SP clones (1.64, 3.8, 3.76 and 3.78) do not produce IL-2 or IL-4, but produce IFN-gamma and IL-12, and they vary in their production of IL-1, RANTES or tumor necrosis factor (TNF)-alpha; (II) DN clones 4.59 and 4.65 produce IL-1 alpha and IFN-gamma only, and fall to produce other cytokines; and (III) DN clones 3.31, 3.71 and 4.19 produce IL-1 alpha, IL-1 beta, IL-2, IL-12, IFN-gamma, RANTES and TNF-alpha. From all the clones examined only DN clones 3.31 and to a lesser degree 4.19 produce IL-4. In vivo tissue localization of clones 3.8, 3.31 and 4.59 shows that these cells distribute into the liver and bone marrow 24 h post i.v. administration. Their accumulation in the liver and bone marrow along with their ability to secrete various cytokines suggest that these cells may influence the generation, differentiation or apoptosis of immune or hematopoietic cells.
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PMID:Cloning, functional activities and in vivo tissue distribution of rat NKR-P1+ TCR alpha beta + cells. 923 13

We have compared the production of the related cytokines IL-13 and IL-4 by T lymphocytes, and the effects of the two cytokines on these cells. IL-13 and IL-4 production differ in a number of respects. IL-13 is produced at higher levels than IL-4 by activated T lymphocytes, and its accumulation in the culture medium can be more prolonged, corresponding partly to differential mRNA accumulation and partly to a preferential depletion of IL-4 from the culture medium. Certain inducing combinations such as PMA and anti-CD28, stimulate high levels of IL-13 and IL-13 mRNA, but little or no IL-4 or IL-4 mRNA. The ratio of IL-13 to IL-4, both at protein and mRNA levels, is higher in CD8+ lymphocyte than in CD4+ lymphocyte populations. Although after in vitro polarization of peripheral blood lymphocytes leading to type 1 and type 2 populations, IL-13 is made principally by cells of a type 2 phenotype, as is IL-4; it can also be produced by type 1 CD4+ and CD8+ T lymphocyte clones making large amounts of IFN-gamma and very little IL-4. IL-13 and IL-4 exert different effects on T lymphocyte functions. IL-13 does not significantly inhibit the IL-2-induced T lymphocyte production of IFN-gamma, RANTES, MIP-1 alpha or MIP-1 beta, nor that of perforin mRNA, as does IL-4. We have also been unable to demonstrate STAT6 activation by IL-13 on T lymphocytes purified in a number of ways, despite strong activation of STAT6 by IL-4 in these cells. This is contrary to some previous reports, but is consistent with the notion that the majority of T lymphocytes lack functional IL-13 receptors. A higher and more prolonged T lymphocyte production of IL-13 than that of IL-4 may thus be permissible because IL-13 does not inhibit T-cell functions. Conversely, sustained IL-13 production may be partly due to the absence of receptor-mediated depletion of this cytokine.
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PMID:The related cytokines interleukin-13 and interleukin-4 are distinguished by differential production and differential effects on T lymphocytes. 926 69

We took advantage of the recently generated 4F7 mAb, which recognizes an epitope expressed on dendritic cells (DC) from different tissues, to freshly isolate and positively sort for these cells and to characterize their cytokine pattern and antigen-presenting capacity in comparison with epidermal Langerhans cells (LC). RT-PCR and Northern blot analyses demonstrated constitutive mRNA expression of MIP-1 gamma, MIP-1 alpha, C10, and IL-1 beta in both 4F7+ DC and LC. Lipopolysaccharide (LPS) treatment resulted in the upregulation of mRNA expression of all four cytokines and in a newly detected signal for TNF alpha. Immunoblot analysis showed constitutive secretion of MIP-1 gamma, with LPS treatment resulting in the upregulation of IL-1 beta production and in newly detected TNF alpha secretion. 4F7+ DC were also shown to express mRNA for the common gamma chain receptor of IL-2 and for the receptor of IL-4. Finally, we demonstrated freshly isolated 4F7+ DC to be equivalent to freshly isolated LC in their capacity to present alloantigen in the mixed leukocyte reaction (MLR) and to process and present purified protein derivative (PPD) to Th1 and Th2 clones. We conclude that 4F7 is a useful marker for positively sorting DC from dermis, spleen, and lymph nodes. Regardless of tissue source, 4F7+ DC exhibit uniform cytokine and antigen-presenting capacity profiles that mimic the properties of freshly isolated epidermal LC.
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PMID:Cytokine expression and antigen-presenting capacity of 4F7+ dendritic cells derived from dermis, spleen, and lymph nodes. 926 19

Fc gamma RIII (CD16), a low affinity FcR which binds IgG-containing immune-complexes, exists under membrane-associated forms and under a soluble form (sFc gamma RIII). The latter, present in biological fluids (serum, saliva), is generated by proteolytic cleavage of the two membrane-associated Fc gamma RIII isoforms, Fc gamma RIII-A (expressed by macrophages and NK cells) and Fc gamma RIII-B (expressed exclusively by neutrophils). Herein we demonstrate that dendritic cells (DCs), generated by culturing monocytes with GM-CSF and IL-4, bind biotinylated recombinant sFc gamma RIII. This binding is specific and involves the complement receptor CR3 (CD11b/CD18) and CR4 (CD11c/CD18). Indeed, preincubation of DCs with anti-CD11b and anti-CD11c mAbs decreased by 52% and 62% respectively the binding with sFc gamma RIII. Moreover, electron microscopy showed that binding of gold-labeled sFc gamma RIII to DCs maintained at 4 degrees C occurred within clathrin-coated pits. Once internalized, at 37 degrees C, sFc gamma RIII entered the endocytic pathway and reached the MHC class II compartments. Furthermore, DCs incubated for 48 h with multivalent sFc gamma RIII expressed increased levels of CD40, CD80, CD86, CD54, CD58, HLA class I and class II molecules and decreased levels of CD23 and CD32. These effects result in an increased capacity of DCs to trigger proliferative responses by CD4+ CD45RA+ allogeneic T cells. RT-PCR amplification demonstrated that incubation of DCs for 20 h in the presence of multivalent sFc gamma RIII induced the appearance of GM-CSF and IL-12 p40 mRNA. Among the cytokines constitutively expressed, IL-1 beta and IL-8 were strongly up-regulated whereas IL-6 and IL-12 p35 mRNA were increased to a lesser extent and the expression of MIP-1 alpha mRNA remained constant. Finally, ELISA tests demonstrated that DCs incubated with multivalent sFc gamma RIII secreted the cytokines IL-1 beta, IL-6, IL-8, GM-CSF and IL-12 p75. Thus, while becoming internalized sFc gamma RIII could affect the capacity of DCs to present antigens and, via the induction of accessory molecules and the release of the IL-12 p75 protein, could initiate Th1 type immune response.
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PMID:Soluble CD16/Fc gamma RIII induces maturation of dendritic cells and production of several cytokines including IL-12. 928 84

Phosphorothioate oligonucleotides with certain sequences or structure motifs can stimulate the immune system. We administered to mice a 27-mer phosphorothioate oligonucleotide (sequence 5'-TCG TCG CTG TCT CCG CTT CTT CTT GCC-3'), which has previously been shown to cause splenomegaly and hypergamma-globulinemia on in vivo administration in mice, and studied the pattern and kinetics of cytokine production at both the splenic mRNA and serum protein levels. Following i.p. administration of 50 mg/kg of oligonucleotide, significant increases in the splenic mRNA levels of IL-6, IL-12p40, IL-1 beta, and IL-1Ra and serum levels of IL-6, IL-12, MIP-1 beta, and MCP-1 were observed. In contrast, no significant differences in splenic mRNA levels of IL-2, IL-4, IL-5, IL-9, IL-13, IL-15, IFN-gamma, or MIF or serum levels of IL-2, IL-4, IL-5, IL-10, IFN-gamma, or GM-CSF were detected. The induction of IL-12 secretion was dependent on the sequence and dose of the oligonucleotides. One oligonucleotide (sequence 5'-GAG AAC GCT CGA CCT TCG AT-3') induced a high level of IL-12 secretion even at 5 mg/kg, whereas another oligonucleotide (sequence 5'-CTC TGC CAC CCA TCT CTC TCC TTC T-3') did not induce significant IL-12 secretion even at 50 mg/kg. IL-12 secretion induced by various doses of oligonucleotide has the same kinetics but differs in magnitude. These studies show a distinct pattern and kinetics of cytokine production following oligonucleotide administration and further demonstrate that cytokine induction is not a general property of phosphorothioate oligonucleotides but is dependent on the sequence and dose of the oligonucleotides.
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PMID:Pattern and kinetics of cytokine production following administration of phosphorothioate oligonucleotides in mice. 936 8

The plasma levels of HIV-1 RNA, tumor necrosis factor alpha (TNF-alpha), soluble receptors type II of TNF-alpha (sTNF-alpha RII), soluble receptors of interleukin-4 (sR IL-4), interleukin-6 (IL-6), soluble receptors of interleukin-6 (sR IL-6), granulocyte macrophage colony stimulating factor (GM-CSF), soluble receptors of GM-CSF (sR GM-CSF), RANTES, MIP-1 alpha and MIP-1 beta were measured in 80 HIV-infected patients. All patients had not been treated previously with antiretroviral drugs and did not present a recent history of opportunistic infection. A statistically significant correlation was found between HIV-1 RNA and TNF-alpha (p = 0.005) or sTNF-alpha RII levels (p < 0.001). RANTES and MIP-1 alpha levels did not correlate with HIV-1 RNA. MIP-1 beta levels were correlated with plasma RNA titers in patients with CD4+ T cells < 200 x 10(6)/l (p = 0.03). MIP-1 alpha and sR IL-4 levels were significantly different according to the CD4+ T cell range (p = 0.003 and p = 0.0002, respectively). GM-CSF and sR GM-CSF were undetectable in each case. These data confirm that HIV-1 replication in the plasma is correlated with TNF-alpha levels, but do not show a clear correlation with levels of the chemokines studied.
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PMID:Correlation between plasma levels of cytokines and HIV-1 RNA copy number in HIV-infected patients. 956 79

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