Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026918 (Mycobacterium)
 52,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Th1 type Cd4+ T cell clone (MH2), which is capable of recognizing purified protein derivative from Mycobacterium tuberculosis (PPD), was examined for its anti-metastatic activity against melanoma. In using an in vitro proliferative assay, MH2 was able to recognize PPD-derived antigen in a major histocompatibility complex class II-restricted manner. MH2 showed neither any natural killer (NK) activity nor cytolytic activity against syngeneic B16 melanoma. This clone produced interferon-gamma, tumor necrosis factor and interleukin-2, but not interleukin-4, when co-cultured with PPD and irradiated syngeneic C57BL/6 spleen cells, suggesting that this clone could thus be assigned to the Th1 subset. An intraperitoneal (i.p.) co-injection of 2 x 10(6) MH2 and 50 micrograms PPD increased the NK activity of the peritoneal exudate cells (PEC) and the percentage of NK1.1+ cells in the PEC. These activated NK cells showed a low but significantly cytolytic activity against B16 melanoma. The augmented NK activity induced by the co-injection of MH2 and PPD was maintained by the weekly additional i.p. injections of PPD alone. Using a murine metastatic model, and i.p. co-injection of MH2 and PPD-induced anti-metastatic activity against B16 melanoma. This anti-metastatic activity was then abrogated by the in vivo administration of anti-asialo GM1 serum. In addition, the NK activity in both peripheral blood and metastatic lungs was significantly augmented in the mice which were co-injected with MH2 and PPD. Taken together, these findings indicate that the in vivo activation of Th1 type CD4+ T cells augmented the NK activity in vivo and thus could potentially be an efficient immunotherapeutic weapon against metastasis of melanoma. These results also imply that adoptive immunotherapy could induce anti-metastatic activity through cytokine production but not through any direct cytolytic activity.
 ...
PMID:Anti-metastatic activity induced by the in vivo activation of purified protein derivative (PPD)-recognizing Th1 type CD4+ T cells. 852 59

Johne's disease is a chronic enteritis of cattle and other ruminant species that is of worldwide economic importance. The cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) have been associated with granuloma formation and wasting in other disease syndromes. The potential role of these cytokines in the development and progression of Johne's disease has not been investigated. Using reverse transcriptase polymerase chain reaction (RT-PCR) and specific bovine oligonucleotide cytokine primers and probes for bovine TNF-alpha and IL-6, we examined the ex vivo expression of mRNA for these inflammatory cytokines in whole blood from healthy cattle. Cytokine mRNA levels increased after a brief incubation of bovine whole blood with Mycobacterium paratuberculosis or its lipoarabinomannan (LAM). Muramyl dipeptide (MDP) and Escherichia coli LPS also stimulated TNF-alpha and IL-6 mRNA expression. Several strains of M. paratuberculosis were tested and found to have similar abilities to stimulate TNF-alpha and IL-6 mRNA expression. Several strains of the closely related Mycobacterium avium, and the unrelated saprophyte, Mycobacterium phlei, had somewhat less ability to stimulate TNF-alpha and IL-6 mRNA expression.
 ...
PMID:Ex vivo induction of TNF-alpha and IL-6 mRNA in bovine whole blood by Mycobacterium paratuberculosis and mycobacterial cell wall components. 855 37

Mycobacterium tuberculosis and its components have been shown to stimulate mononuclear phagocytes in vitro to release interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6). Animal models of tuberculosis (TB) also demonstrate the presence of cytokines in granulomas. We hypothesized that bronchoalveolar lavage (BAL) cells from patients with pulmonary TB would have increased spontaneous release of IL-1 beta, IL-6, and TNF-alpha and would have a concomitant alveolitis. We performed BAL on 26 patients with active TB and on six normal volunteers. BAL fluid from radiographically involved and uninvolved sites was evaluated separately for cell types and the spontaneous release of cytokines. The alveolar inflammation in involved sites was characterized by an increase in lymphocytes (miliary TB, 38 +/- 10%; involved sites, 22 +/- 4%; uninvolved sites, 13 +/- 2%; normal, 5 +/- 2%) and neutrophils (involved sites, 21 +/- 7%; uninvolved sites, 3 +/- 2%). There was a significant increase in the spontaneous release of IL-1 beta (501 +/- 280 pg/ml), TNF-alpha (782 +/- 165 pg/ml), and IL-6 (473 +/- 157 pg/ml) from involved sites of TB patients that was 5- to 20-fold greater than uninvolved sites, normal controls, or miliary TB. Northern analysis revealed increased gene expression of IL-1 beta, TNF-alpha, and IL-6 from the involved sites from two patients with TB compared with two negative controls. We conclude that BAL cells, especially alveolar macrophages, are activated in the alveolar inflammation of active TB and spontaneously release increased quantities of IL-1 beta, IL-6, and TNF-alpha, and that these cytokines are likely to be involved in directing granuloma formation and control of M. tuberculosis infection.
 ...
PMID:Increased release of interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha by bronchoalveolar cells lavaged from involved sites in pulmonary tuberculosis. 856 35

Interleukin-10 (IL-10) inhibits intracellular Mycobacterium avium killing by cytokine-activated murine macrophages and may have a role in pathogenesis. Cytokine activities in supernatants of M. avium-infected human monocytes were maximal at 6-24 h for tumor necrosis factor (TNF)-alpha and 24-48 h for IL-10. TNF-alpha and IL-10 production increased with increasing M. avium-to-monocyte infection ratios (20:1 to 200:1). TNF-alpha production by monocytes infected with smooth, domed, and opaque organisms at 200:1 exceeded that of monocytes infected with smooth, flat, and transparent M. avium (P < .01). IL-10 induction demonstrated considerable strain-to-strain variability and did not correlate with intracellular M. avium growth. IL-10 significantly inhibited TNF-alpha, IL-1 beta, and IL-6 production by M. avium-infected monocytes. Coculturing monocytes with IL-10 after M. avium infection did not affect intracellular M. avium growth. Differential induction of TNF-alpha may be a factor in the intracellular growth of M. avium in human monocytes. IL-10, however, played no apparent role in pathogenicity in this model.
 ...
PMID:Evidence against a role for interleukin-10 in the regulation of growth of Mycobacterium avium in human monocytes. 856 3

To investigate whether infection with Mycobacterium avium modifies the cytokine response of human macrophages (Mphi) to lipopolysaccharide (LPS), the release of interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha was determined in infected and uninfected Mphi, unstimulated or stimulated with LPS. In unstimulated Mphi, the release of IL-1 beta and IL-6 increased with the progress of infection while that of TNF-alpha progressively decreased. When Mphi were stimulated with LPS, IL-1 beta and IL-6 levels were always higher in infected than in uninfected cells, but levels of TNF-alpha significantly decreased in infected Mphi. A similar trend was obtained for TNF-alpha mRNA expression. Altogether, these results indicate that infected Mphi react to LPS stimulus with enhanced levels of IL-1 beta and IL-6 but are unable to restore the production of TNF-alpha impaired by the growth of the intracellular mycobacteria.
 ...
PMID:Late acquisition of hyporesponsiveness to lipopolysaccharide by Mycobacterium avium-infected human macrophages in producing tumor necrosis factor-alpha but not interleukin-1 beta and -6. 860 46

Multinucleated giant cells (MGC) have been long recognized as a histopathologic feature of tuberculosis, yet little is known about the underlying mechanism of tubercle bacillus-induced formation of these fused macrophages. The main purpose of this study was to characterize cellular mechanisms involved in MGC formation of swine microglia, the resident macrophages of the brain, in cultures containing nonopsonized Mycobacterium bovis. Within 2 h of incubation, MGC were readily detected in these cultures by light and transmission electron microscopy. MGC formation was blocked by anti-CD14 and anti-CD18 antibodies and by thalidomide, a potent inhibitor of tumor necrosis factor-alpha (TNF-alpha) production my microglia. Also, TNF-alpha alone induced MGC formation. These findings suggest that two microglial cell receptors, CD14 and a beta2 integrin, and the cytokine TNF-alpha participate in M. bovis-induced swine microglial MGC formation.
 ...
PMID:Multinucleated giant cell formation of swine microglia induced by Mycobacterium bovis. 862 72

We studied the involvement of reactive oxygen intermediates and reactive nitrogen intermediates in the bacteriostasis of two Mycobacterium avium strains differing in virulence by resident peritoneal macrophages. We found that both the highly virulent strain (25291) and the low-virulence strain (1983) of M. avium induced superoxide production but inhibited nitrite production in vitro. This inhibition was due to the production of superoxide, a nitric oxide scavenger. The stimulation of superoxide production was two- to fivefold higher in strain 1983-infected than in strain 25291-infected resident peritoneal macrophages and was independent of contaminating T cells or NK cells. Superoxide secretion was dependent on the tumor necrosis factor (TNF) produced endogenously by the macrophages. This was also true when macrophages were isolated from infected mice. Addition of TNF to the infected resident peritoneal macrophages caused only a slight, albeit significant, increase in superoxide production by strain 25291-infected macrophages. Incubation of resident peritoneal macrophages with different scavengers of reactive oxygen intermediates showed that strain 1983 was susceptible to hydrogen peroxide produced by resident peritoneal macrophages. Strain 25291 was shown to decrease superoxide secretion inside heavily infected bone marrow-derived macrophages. This strain was also shown to be a better trigger for production of reactive oxygen intermediates than strain 1983. In summary, strain 1983 induced high levels of TNF synthesis that acted in an autocrine fashion to stimulate production of reactive oxygen intermediates by macrophages leading to growth restriction mediated by hydrogen peroxide. The highly virulent strain 25291 induced low levels of TNF synthesis, and therefore little reactive oxygen intermediate production, and could also inhibit superoxide production by the infected macrophages.
 ...
PMID:Involvement of reactive oxygen intermediates in tumor necrosis factor alpha-dependent bacteriostasis of Mycobacterium avium. 875 57

Previously we demonstrated that treatment of mice with either UVB radiation or supernatants derived from UVB-irradiated PAM 212 keratinocytes decreased the induction of the delayed-type hypersensitivity (DTH) response to Mycobacterium bovis bacillus Calmette-Guerin (BCG), impaired the clearance of bacteria from their lymphoid organs and also altered macrophage functions. In order to characterize the cytokines involved in these phenomena, UV-irradiated mice were injected with antibodies to interleukin-10 (IL-10), transforming growth factor-beta 1 (TGF-beta 1), or tumor necrosis factor-alpha (TNF-alpha). Injection of UVB-irradiated mice with anti-IL-10 immediately after UV irradiation restored the DTH response and reversed the UV-induced inhibition of bacterial clearance. Injection of UV-irradiated mice with anti-TGF-beta only partially restored the DTH response although it allowed a better clearance of BCG than injection of mice with the control antibody. In contrast, injection of anti-TNF-alpha did not affect the UVB-induced suppression of DTH or impaired bacterial clearance. Similarly, the ability of macrophages to phagocytose BCG and kill the intracellular organisms was restored to almost normal levels after injecting UV-irradiated mice with antibodies specific for IL-10 or TGF-beta. Injection of mice with either recombinant IL-10 or TGF-beta mimicked the effect of whole-body UV irradiation on immune function. These results suggest that IL-10 has a major role in UV-induced suppression of both DTH to BCG and impairment in the clearance of bacteria and that TGF-beta has a more significant role in blocking bacterial clearance. Furthermore, these cytokines seem to modulate immune responses by altering macrophage functions in UVB-irradiated mice.
 ...
PMID:Mechanism of UVB-induced suppression of the immune response to Mycobacterium bovis bacillus Calmette-Guerin: role of cytokines on macrophage function. 876 May 65

The growth of Mycobacterium microti was inhibited within J774A.1 macrophage cells activated with either interferon-gamma or tumor necrosis factor-alpha. Activation with interferon-gamma or tumor necrosis factor-alpha alone did not stimulate the production of nitrite in J774A.1 cells. Interferon-gamma but not tumor necrosis factor-alpha increased the production of hydrogen peroxide in a concentration dependent manner but scavengers of reactive oxygen species did not influence the growth inhibiting effect of interferon-gamma within J774A.1 cells. Both interferon-gamma and tumor necrosis factor-alpha enhanced the fusion of M. microti containing phagosomes with lysosomes and the ultimate degradation of bacteria. Our results showed that growth inhibition of M. microti within interferon-gamma or tumor necrosis factor-alpha stimulated J774A.1 cells was independent of reactive oxygen intermediate and reactive nitrogen intermediate production.
 ...
PMID:Attempts to characterize the mechanisms involved in the growth inhibition of Mycobacterium microti in interferon-gamma or tumor necrosis factor-alpha activated J774A.1 cells. 876 80

Prostanoids, including prostaglandin E2 (PGE2), suppress macrophage effector functions against Mycobacterium tuberculosis. PGE2 production by monocytes infected with Mycobacterium avium complex (MAC) and its effects on intracellular mycobacterial growth were examined. Freshly obtained monocytes from healthy subjects were stimulated with lipopolysaccharide or 10(7) organisms/mL of 4 MAC strains. PGE2 production in monocyte supernatants peaked at 48 h. Significantly higher levels of PGE2 were produced by monocytes infected with the mixed rough-smooth, flat, and transparent (SmT) morphotype strain 86m2096 (26.8 +/- 5.2 ng/mL) than by the more virulent LR114 SmT morphotype strain (2.4 +/- 0.6 ng/mL; P < .05, paired t test). When infected monocytes were incubated with 1 microgram/mL indomethacin (IM) for 2 days and then further stimulated with interferon-gamma, no effect on intracellular MAC growth was evident. IM increased tumor necrosis factor-alpha (1.7 +/- 0.4 vs. 2.3 +/- 0.3 ng/mL; P = .005, paired t test) but not interleukin-1 beta (8.2 +/- 1.7 vs. 8.7 +/- 2.1 ng/mL, P = .34) production by monocytes stimulated with lipopolysaccharide. These data suggest that MAC-induced PGE2 expression may modulate cytokine production and intracellular parasitism.
 ...
PMID:Induction of prostaglandin E2 by human monocytes infected with Mycobacterium avium complex--modulation of cytokine expression. 884 20


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