Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026916 (MAC)
 5,226 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to verify the participation of some cytokines in the expression of the suppressor activity of splenic macrophages (M phi s) induced by Mycobacterium avium complex (MAC) infection, we studied whether anticytokine antibodies were capable of blocking their suppressor activity against concanavalin A (ConA)-induced mitogenesis of splenocytes (SPCs). When either anti-tumor necrosis factor (TNF), anti-transforming growth factor-beta (TGF-beta), or anti-interferon-gamma (IFN-gamma) antibody was added to culture medium, suppressor activity was markedly reduced, in the order of anti-TNF, anti-IFN-gamma, and anti-TGF-beta antibodies. By contrast, neither anti-interleukin-6 (IL-6) nor anti-IL-10 antibody exerted such a blocking effect. Therefore, TNF, IFN-gamma, and TGF-beta seem to be related to the full display of the suppressor function of MAC-induced M phi s. However, TNF-alpha and IFN-gamma but not TGF-beta were substantially lacking in inhibitory action against SPC mitogenesis, when added exogenously. Hence, it is unlikely that TNF-alpha and INF-gamma directly modulated the proliferative response of T cells. On the other hand, both TNF-alpha and IFN-gamma potentiated the effector function of the suppressor M phi s. Because their suppressor activity was severely reduced by NG-monomethyl-L-arginine and aminoguanidine, nitric oxide (NO) synthase inhibitors, an NO-dependent mechanism is important for the expression of the immunosuppressive function of MAC-induced M phi s. Moreover, because these M phi s seem to produce a substantial amount of TNF-alpha in membrane-bound form, cell-to-cell contact might be needed for efficient expression of their suppressor action on target T cells.
 ...
PMID:The role of tumor necrosis factor, interferon-gamma, transforming growth factor-beta, and nitric oxide in the expression of immunosuppressive functions of splenic macrophages induced by Mycobacterium avium complex infection. 749 69

Although various antimicrobial drugs show appreciable bactericidal activity in the early phase (2 to 4 weeks after infection) of Mycobacterium avium complex (MAC) infections in mice, no drug, as far as we know, can continue to exert the growth inhibiting activity against the bacteria at the site of infection in the progressed stage. Here, we studied the mechanisms of the bacterial regrowth which usually starts around 2-4 weeks after infection. First, the changes in the level of TNF-alpha, IFN-gamma, IL-6 and IL-10 in the lungs and spleen during the course of MAC infections was examined. Tissue levels of TNF-alpha and IL-10 increased around weeks 2 to 4, then rapidly decreased thereafter, and returned to the normal levels by week 8, while levels of IFN-gamma and IL-6 remained very low throughout the observation period. In this experiment, the bacterial CFUs rapidly decreased during the first 2 weeks of the treatment with a rifamycin derivative, KRM-1648, and thereafter the regrowth of the organisms was observed even in mice treated continuously with KRM-1648, although the rate of bacterial growth in the treated mice was much lower than in untreated control mice. Second, effect of either anti-TGF-beta or anti-IL-10 antibody on intracellular growth of MAC in human monocytes cultured in vitro in the medium with or without addition of TNF-alpha or IFN-gamma were examined. Anti-TGF-beta and anti-IL-10 antibodies potently reduced the bacterial growth in monocytes. Effects of TNF-alpha and IFN-gamma in reducing the bacterial growth was potentiated by the addition of either anti-TGF-beta or anti-IL-10 antibody. Third, anti-IL-10 antibody augmented to some extent the chemotherapeutic efficacy of KRM-1648 against MAC infection, when the drug was given to mice at weeks 2 and 4 after infection. From these results, it is suggested that IL-10 derived from MAC-infected macrophages in response to stimulation with some bacterial components, such as lipoarabinomannan, might downregulate the antimicrobial function of host macrophages against MAC.
 ...
PMID:[Mechanism of bacterial regrowth at the sites of infection in Mycobacterium avium complex-infected mice during treatment with chemotherapeutic agents]. 855 14

Organisms of the Mycobacterium avium complex survive the hostile environment of their host cells, the macrophages, and evade immune response, in part, by interfering with processing and presentation of antigen. We studied the effect of infection with M. avium on the expression of the costimulatory/adhesion molecules (referred to herein as accessory molecules) because generating an efficient T cell response requires both the recognition of processed antigen and the participation of accessory molecules. Human peripheral blood monocytes displayed reduced levels of CD54, CD58, and CD86 molecules 1 day after in vitro infection. The reduction in the expression of accessory molecules was not mediated by endogenous IL-10 or prostaglandin because monocytes infected in the presence of either anti-IL-10 neutralizing antibody or indomethacin did not express normal levels of surface CD54, CD58, and CD86 molecules. Consistent with these phenotypic changes, M. avium-infected monocytes were less effective in supporting Ag-independent proliferation of autologous CD4+ T cells.
 ...
PMID:Mycobacterium avium reduces expression of costimulatory/adhesion molecules by human monocytes. 907 Mar 21

In murine infections due to Mycobacterium avium complex (MAC), bacterial regrowth of the pathogens is frequently encountered in the relatively late phase of infection even in mice receiving daily treatments with antimicrobial agents including rifamycins and macrolides. In this case, the bacterial regrowth is usually accompanied by concomitant increase in the tissue levels of IL-10 and transforming growth factor-beta (TGF-beta), well known immunosuppressive cytokines. In this context, it is of interest to note recent findings that steroidal anti-inflammatory drugs up-regulate TGF-beta production from T lymphocytes, thereby suggesting participation of immunosuppressive cytokines in the expression of their anti-inflammatory activity. In this study, we examined the effects of various anti-inflammatory drugs including glucocorticoids and non-steroidal anti-inflammatory drugs (NSAID) on in-vitro IL-10 production of murine peritoneal macrophages (M phi s) infected with MAC organisms. When the IL-10 production by MAC-infected M phi s was measured in terms of protein and mRNA expression of the cytokine using ELISA and RT-PCR assays, the following results were obtained. First, the IL-10 production into M phi culture fluids was temporarily increased around days 1 to 3, thereafter gradually declined, and returned to normal by day 14. Secondly, IL-10 mRNA expression of M phi s was rapidly induced after MAC-infection and the maximum level of the mRNA expression was achieved at 2 hr. Thereafter, IL-10 mRNA expression ceased rapidly and returned to normal by 24 hr. Thirdly, the majority of test anti-inflammatory drugs, not only glucocorticoids but also NSAID, were found to up-regulate the IL-10 production of MAC-infected M phi s, suggesting some possible roles of IL-10 in the expression of the anti-inflammatory activities of these agents.
 ...
PMID:[Effects of various steroidal and non-steroidal anti-inflammatory drugs on in-vitro IL-10 production of murine peritoneal macrophages infected with Mycobacterium avium complex]. 933 28

Patients with advanced human immunodeficiency virus (HIV) infection are susceptible to infections with Mycobacterium avium complex (MAC). Interleukin (IL)-10 may impair immunity to MAC; therefore, the effect of different MAC preparations on IL-10 production was examined in mononuclear cell cultures from HIV-infected patients. IL-10 levels in cultures for 26 patients were higher than those in 20 control cultures. The highest IL-10 levels were found in cultures from patients with the most advanced HIV disease. Monocytes were the major IL-10 producers, while little IL-10 could be attributed to Th2 lymphocytes. Cultures for patients produced reduced levels of tumor necrosis factor-alpha and normal levels of IL-12; the production of these cytokines increased after neutralization of IL-10. Circulating IL-10 was higher in HIV-infected patients than in controls, with the highest levels in the AIDS group. Elevated monocyte/macrophage-derived IL-10 production may contribute to the high susceptibility to MAC infection seen in patients with advanced HIV disease.
 ...
PMID:Enhanced interleukin-10 production in response to Mycobacterium avium products in mononuclear cells from patients with human immunodeficiency virus infection. 949 36

We have previously shown that tonsil tissue both from children with tonsillar hypertrophy and recurrent tonsillitis is colonized and invaded by Haemophilus influenzae and Streptococcus pyogenes group A. In order to evaluate if these bacteria are involved in the immunopathogenesis of these two conditions, tonsillar cells from both groups were stimulated in vitro with intact, heat-inactivated H. influenzae or S. pyogenes A. The immunoreactivity was evaluated by assessing the induction of cytokine production (IL-1 alpha, IL-1 beta, TNF-alpha, IL-6, IL-8, IL-2, IFN-gamma, IL-4, TNF-beta and IL-10), which was detected at the single-cell level. All cytokines studied except IL-4 were induced in both groups after stimulation with H. influenzae or S. pyogenes A. The dominating cytokines were IL-1 beta, IFN-gamma and TNF-beta. No major differences in the cytokine pattern or number of cytokine-producing cells were noticed between the two patient cohorts after H. influenzae stimulation. Activation by S. pyogenes A bacteria gave rise to higher frequencies of IFN-gamma- and TNF-beta-synthesizing cells in the recurrent tonsillitis group. The incidence of CD4-, CD8-positive T cells and CD40-positive B cells was comparable between the two groups while the MAC-387-positive macrophages were significantly higher in the recurrent tonsillitis groups. In conclusion, a Th1 type of cytokine response was found in both groups following stimulation with H. influenzae or S. pyogenes A.
 ...
PMID:Haemophilus influenzae and Streptococcus pyogenes group A challenge induce a Th1 type of cytokine response in cells obtained from tonsillar hypertrophy and recurrent tonsillitis. 951 80

The establishment of a primary trigeminal ganglion (TG) cell culture latently infected with herpes simplex virus type 1 (HSV-1) has been useful in studying stress-induced reactivation of the latent virus. However, the immune profile of this culture system prior to and after stress has never been established. In the present manuscript, cytokine and chemokine production were measured in primary cultures of TG cells obtained from uninfected and HSV-1 latently infected mice. Supernates from TG cell cultures contained detectable interleukin (IL)-6 but not IL-1beta, IL-2, IL-10, interferon (IFN)-gamma or tumor necrosis factor (TNF)-alpha as determined by ELISA. The basal level of IL-6 in uninfected TG cell cultures was 20.5 +/- 2.3 ng/ml, whereas latently infected TG cells produced significantly less IL-6 (12.1 +/- 1.9 ng/ml). Supernates from TG cell cultures also contained detectable levels of C-10, MCP-1 and eotaxin but little to no MIP-1alpha, MIP-1beta, or MIP-2. While there were no differences in the basal level of MCP-1 and eotaxin in TG cell cultures from HSV-1-infected and uninfected mice, C10 levels were significantly higher in TG cultures originating from infected mice compared to uninfected ones (5.86 +/- 0.61 ng/ml compared to 1.18 +/- 0.16 ng/ml). Hyperthermic stress (43 degrees C, 180 min), which induces reactivation of latent HSV-1 from TG cell cultures, significantly reduced IL-6 and C-10 levels from both uninfected and latently infected TG cell cultures. However, there was no correlation between cytokine/chemokine levels and HSV-1 reactivation. Immunofluorescent studies showed TG cell cultures contained 10% MAC-3+ staining cells (macrophage specific) but no dendritic cells. By comparison, cells from freshly isolated TG contained 6% positive dendritic cells but < 1% MAC-3 + cells. Both in vivo and in vitro TG consisted of a low percentage of CD3+ and CD8+ cells. Hyperthermic stress (43 degrees C for 3 h) eliminated the lymphocyte population as determined by RT-PCR. Whereas no spontaneous reactivation has been reported in mice, spontaneous reactivation occurred in 4.5% (10/220) of TG cell cultures surveyed over a 20 day period. Collectively, the dichotomy between HSV-1 replication and reactivation comparing the in vitro and in vivo HSV-1 latency models may reside, in part, to the differences in the levels of cytokines, chemokines and immune cell populations within the microenvironment of the in vitro and in vivo TG.
 ...
PMID:Cytokine and chemokine production in HSV-1 latently infected trigeminal ganglion cell cultures: effects of hyperthermic stress. 963 Jan 59

To examine the potential pathogenic role of IL-10 in HIV infection, we measured serum IL-10 levels in 51 HIV-infected patients and 23 healthy controls both on cross-sectional and longitudinal testing. All clinical groups (Centers for Disease Control (CDC) categories) of HIV-infected patients had significantly higher circulating IL-10 levels than controls, with the highest levels among the AIDS patients, particularly in patients with ongoing Mycobacterium avium complex (MAC) infection. Among 32 HIV-infected patients followed with longitudinal testing (median observation time 39 months), patients with disease progression had increasing IL-10 levels in serum, in contrast to non-progressing patients where levels were stable. While both IL-10 and tumour necrosis factor-alpha (TNF-alpha) increased in patients with disease progression, the IL-10/TNF-alpha ratio decreased in these patients, suggesting imbalance between these two cytokines. Finally, we found that highly active anti-retroviral therapy (HAART) induced a significant, gradual decrease in IL-10 levels but without normalization. These findings suggest a pathogenic role for IL-10 in HIV infection, and may suggest a possible role for immunomodulating therapy which down-regulates IL-10 activity in addition to concomitant potent anti-retroviral therapy in HIV-infected patients.
 ...
PMID:IL-10 in HIV infection: increasing serum IL-10 levels with disease progression--down-regulatory effect of potent anti-retroviral therapy. 1020 14

Interleukin-15 (IL-15) is a potent regulator of T-, B-, and natural killer cell proliferation and displays unusually tight controls of secretion. Even though IL-15 mRNA is constitutively expressed in monocytes/macrophages and is upregulated by a variety of stimuli, evidence for IL-15 cytokine secretion is only found exceptionally, eg, conditions of pathological, chronic inflammation. This raises the possibility that monocytes express membrane-bound IL-15 rather than secrete it. The current study explores this hypothesis. We demonstrate here that biologically active IL-15 is indeed detectable in a constitutively expressed, membrane-bound form on normal human monocytes, as well as on monocytic cell lines (MONO-MAC-6, THP-1, and U937), but not on human T or B cells (MT4, M9, C5966, JURKAT, DAUDI, RAJI, and Epstein-Barr virus-immortalized B-cell clones). Furthermore, cell surface-bound IL-15 is upregulated upon interferon-gamma stimulation. Interestingly, monocyte/macrophage inhibitory cytokines such as IL-4 and IL-13 fail to downregulate both constitutive and induced cell-surface expression of IL-15. Membrane-bound IL-15 does not elute with acetate buffer or trypsin treatment, suggesting that it is an integral membrane protein and that it is not associated with the IL-15 receptor complex. Finally, membrane-bound IL-15 stimulates T lymphocytes to proliferate in vitro, indicating that it is biologically active. These findings enlist IL-15 in the fairly small family of cytokines for which the presence of a biologically active membrane-bound form has been demonstrated (eg, IL-1, tumor necrosis factor-alpha, and IL-10) and invites the speculation that most of the biological effects of IL-15 under physiological conditions are exerted by the cell surface-bound form.
 ...
PMID:Human monocytes constitutively express membrane-bound, biologically active, and interferon-gamma-upregulated interleukin-15. 1023 6

We have investigated the protein expression of the chemokine monocyte chemotactic/chemoattractant protein-1 (MCP-1) in various human myelomonocytic leukemia cell lines. Applying specific ELISA, we demonstrated that this chemokine is produced constitutively by the cell lines HL-60, ML-2, MONO-MAC-6 and MUTZ-3 ranging between 440 and 1400 pg/ml MCP-1 per million cells. In the culture medium of two other unstimulated cell lines, MONO-MAC-1 and THP-1, almost no MCP-1 was detected. Stimulation of HL-60 and MONO-MAC-6 with lipopolysaccharide (LPS), and stimulation of ML-2 and MUTZ-3 with 12-tetradecanoyl phorbol 13-acetate (TPA) dramatically increased the MCP-1 level in the culture medium. The highest amount of MCP-1 (> 80 ng/ml within 24 h) was achieved by TPA stimulation of MUTZ-3 cells. Out of 15 cytokines tested for induction or enhancement of MCP-1 secretion, interleukin-3 (IL-3), IL-6, interferon-gamma (IFN-gamma), granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF) and tumor necrosis factor (TNFalpha) were able to augment (twofold to 12-fold) the MCP-1 level in the culture medium of MONO-MAC-6 cells. While the antinflammatory cytokines IL-4, IL-10 and IL-13 failed to suppress MCP-1 secretion, the glucocorticoid dexamethasone strongly inhibited the MCP-1 production of unstimulated and stimulated MONO-MAC-6 cells. Thus, several regulatory elements are involved in MCP-1 secretion. Despite the quantitative differences of MCP-1 production among the cell lines analyzed, our results demonstrated a constitutive secretion in differentiation-arrested myelomonocytic leukemia cell lines and emphasize the usefulness of these malignant cell lines as models to study MCP-1 secretion and regulation.
 ...
PMID:Constitutive protein expression of monocyte chemotactic protein-1 (MCP-1) by myelomonocytic cell lines and regulation of the secretion by anti- and proinflammatory stimuli. 1047 24


1 2 3 Next >>