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)

Downregulation of pro-inflammatory events in the immune response to Mycobacterium tuberculosis is critical to prevent host tissue injury. Interleukin (IL-)10 is an important anti-inflammatory cytokine secreted in human tuberculosis but little is known about the control of such IL-10 release. Using an established cellular model, we measured IL-10 secretion after phagocytosis of M. tuberculosis. Phagocytosis of M. tuberculosis but not of inert latex beads by human monocytic (THP-1) cells resulted in IL-10 secretion maximal at 24 h. The magnitude and kinetics of IL-10 secretion were distinct from IL-10 secretion after phagocytosis of yeast-derived zymosan and depended on transcriptional activity and protein synthesis in infected monocytes. IL-10 secretion was decreased in a dose-dependent manner by specific inhibitors of tyrosine kinases, protein kinase (PK) C and PKA. Inhibition of more than one pathway did not result in further synergistic or additive reduction in IL-10 secretion. Finally, specific neutralising antibody directed against IL-10 demonstrated that IL-10 secreted by infected monocytic cells did not block autologous IL-8 secretion.
Cytokine 2000 May
PMID:Regulation of IL-10 secretion after phagocytosis of Mycobacterium tuberculosis by human monocytic cells. 1085 63

Cervine interferon gamma (IFN-gamma) was cloned and expressed using an Escherichia coli expression system pET-32. The expressed protein contained a 6 histidine purification tag and an 11 kDa thioredoxin fusion partner 5' to the IFN-gamma molecule. The ability of IFN-gamma to inhibit the killing of Madin-Darby bovine kidney cells by Semliki forest virus was used as a measure of the bioactivity of the recombinant cervine IFN-gamma (rIFN-gamma). It was shown that the presence of the thioredoxin fusion partner 5' to the IFN-gamma molecule did not affect its biological activity. As in the mouse model, it was shown that cervine rIFN-gamma was able to down-regulate the transcription of interleukin 10 mRNA while up-regulating the transcription of interleukin 12 mRNA in lipopolysaccharide-sensitized, peripheral blood mononuclear cells. A prototype ELISA was tested for its ability to detect both recombinant and native IFN-gamma. The ELISA was able to detect rIFN-gamma at concentrations greater than 100 pg/ml. It was also used to detect native IFN-gamma produced by peripheral blood lymphocytes from Mycobacterium bovis infected or vaccinated deer after in vitro restimulation with antigen. The rIFN-gamma and the cervine IFN-gamma specific ELISA provide valuable tools with which to study important zoonotic infections in farmed and wild deer.
Cytokine 2000 Aug
PMID:The production and biological assessment of cervine interferon gamma. 1093 Feb 98

A genetic component to human mycobacterial disease susceptibility has long been postulated. Over the past five years, mutations in the interferon-gamma (IFNgamma) receptor, IL-12 receptor beta1 (IL-12Rbeta1), and IL-12 p40 genes have been recognized. These mutations are associated with heightened susceptibility to disease caused by intracellular pathogens including nontuberculous mycobacteria, vaccine-associated bacille Calmette Guerin (BCG), Salmonella species, and some viruses. We describe the genotype-phenotype correlations in IFNgamma receptor, IL-12Rbeta1, and IL-12 p40 deficiency, and discuss how study of these diseases has enhanced knowledge of human host defense against mycobacteria and other intracellular pathogens.
Cytokine Growth Factor Rev 2000 Dec
PMID:Interferon-gamma and interleukin-12 pathway defects and human disease. 1095 79

IL-17 is a T cell cytokine with a complex and important role in the immune system. It has been detected in rheumatoid arthritis (RA) synovial membrane and found to stimulate the production of the proinflammatory cytokines IL-6, IL-8, tumour necrosis factor-alpha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in vitro. To date, there are few data available on the agents that stimulate IL-17 production. We therefore investigated the in vitro IL-17 response to a variety of mitogens and antigens, and compared the IL-17 response to interferon-gamma (IFN-gamma), IL-4, IL-10 and TNF-alpha. In this study we used a type-0 antigen, tetanus toxoid (TT), a type-1 antigen, PPD from Mycobacterium tuberculosis, a potential type-2 rye grass (RG) antigen (Lol I) and an autoantigen SS.B (La), to stimulate PBMC from healthy controls. Cytokine mRNA was measured using semiquantitative reverse transcriptase-polymerase chain reaction and cytokine protein measured using specific ELISA techniques, while the frequency of IL-17-producing T cells was determined by flow cytometry. The mitogens concanavalin A, phytohaemagglutinin and phorbol myristate acetate/ionomycin induced a significant increase in IL-17, with the highest levels being produced by anti-CD3/anti-CD28 stimulation. The antigens TT and PPD significantly increased IL-17 mRNA expression over time, but failed to have such an effect at the protein level. IL-17 protein was also detectable in both antigen-specific (TT, SS. B) and non-specific T cell clones, but at levels lower than IFN-gamma. IL-17 production did not correlate with either the type-1 cytokine IFN-gamma or TNF-alpha or the type-2 cytokine IL-4 or IL-10 at either the mRNA or protein level.
 ...
PMID:Antigen-induced IL-17 response in the peripheral blood mononuclear cells (PBMC) of healthy controls. 1101 16

Mycobacteria-induced in vitro events reflecting human tuberculosis can contribute to the evaluation of the pathogenesis of Mycobacterium tuberculosis (MTB). In this study, we propose such an in vitro method based on live mycobacteria-induced cytotoxicity to human cell lines. When human lung-derived normal fibroblast cell line MRC-5 was infected with various strains of mycobacteria (M. tuberculosis H(37)Rv and H(37) Ra, Mycobacterium avium 427S and 2151SmO, and Mycobacterium bovis BCG Pasteur and Tokyo), the fibroblasts were killed by mycobacteria according to the degree of virulence. Other human originated macrophage (U-937, THP-1), myeloid (HL-60), and epithelial carcinoma (A549) cell lines exhibited a similar cytotoxic response to virulent mycobacteria. MRC-5 was most susceptible to virulent mycobacteria among various human cell lines examined. The cytotoxicity was enhanced by the proinflammatory cytokines, interleukin-1 (IL-1) and tumor necrosis factor-a (TNF-alpha), which in the absence of mycobacteria stimulate the growth of normal human fibroblasts. This in vitro evaluation system was applied to clinical isolates of drug-sensitive MTB (DS-MTB), drug-resistant MTB (DR-MTB) including multidrug-resistant (MDR-MTB), and M. avium complex (MAC). MTB strains (n = 24) exhibited strong cytotoxic activity, but MAC strains (n = 5) had only weak activity. Furthermore, there was no significant difference in cytotoxicity between DS-MTB (n = 11) and DR-MTB (n = 13). Collectively, these results suggest that this new in vitro system is useful for evaluating the pathogenesis of mycobacteria and that there was no difference in the pathogenesis between drug-susceptible and drug-resistant clinical isolates.
J Interferon Cytokine Res 2001 Mar
PMID:Interleukin-1 or tumor necrosis factor-alpha augmented the cytotoxic effect of mycobacteria on human fibroblasts: application to evaluation of pathogenesis of clinical isolates of Mycobacterium tuberculosis and M. avium complex. 1133 Oct 42

Cytokine gene expression in ileal tissues of cattle infected with Mycobacterium paratuberculosis was evaluated. The effects of infection with M. paratuberculosis on cytokine production may influence immune regulation at the site of colonization, resulting in the chronic inflammatory state associated with the latter stages of this disease. Ileal samples were obtained at necropsy from noninfected control cows (n=8) and clinically infected cows (n=7) and processed for immunohistochemistry and in situ hybridization. Cows infected with M. paratuberculosis were in the latter stages of disease with clinical signs such as weight loss, watery diarrhea, and inappetence. Among cytokines we studied, interleukin-1alpha (IL-1alpha), IL-1beta, IL-6, and interferon-gamma (IFN-gamma) were expressed significantly more in infected animals than in noninfected control animals. The expression of tumor necrosis factor-alpha (TNF-alpha), however, was not different between the two groups of cattle. In addition, immunohistochemical staining demonstrated that the number of resident macrophages in the ileum of infected animals was three times greater than that of noninfected cows. In contrast to this, ileal tissues from noninfected control animals contained 1.5 times more neutrophils than the ileal tissues from cows infected with M. paratuberculosis. These data demonstrate that localized ileal cytokine production is different between cows chronically infected with M. paratuberculosis and noninfected control cows.
 ...
PMID:Cytokine gene expression in ileal tissues of cattle infected with Mycobacterium paratuberculosis. 1155 95

Cytokine and chemokine responses during anamnestic type-1 and type-2 lung granuloma formation were evaluated in mice at 6,12,18 and 24-months of age. Lesions were induced by embolizing Sepharose beads coupled to Mycobacterium bovis purified protein derivative or soluble Schistosoma mansoni egg antigens. Type-1 inflammation was reduced by 18 months, whereas type-2 granulomas not until 24 months of age. In type-1 draining lymph nodes cultures, interferon-gamma (IFNgamma) declined to a nadir by 18, and then partly recovered at 24 months. In contrast, IL-4 was not significantly impaired in type-2 cultures until 24 months. Type-1 and 2 node cultures also displayed decreased IL-13, but paradoxically enhanced IL-5 production at 24 months. Chemokine transcripts in granulomatous lungs displayed age-related alterations. In the type-1 response, CXCL9 (monokine-induced by IFNgamma) declined with age then partly recovered at 24 months parallelling lymph node IFNgamma levels. Transcripts for MIP-2/CXCL2, IP-10/CXCL10, MCP-1/CCL2, and MCP-5/CCL12 increased at 24 months. In the type-2 response MCP-1/CCL2, MCP-3/CCL7, MCP-5/CCL12 and TARC/CCL17 collapsed at 24 months paralleling local IL-4 transcript levels, yet some chemokine transcripts such as KC/CXCL1 and eotaxin/CCL11 were unaffected. These findings suggest that cytokine and chemokine responses degrade differentially with age shifting Th1/Th2 crossregulatory pressures and local expression of chemokines.
 ...
PMID:Differential effects of ageing on cytokine and chemokine responses during type-1 (mycobacterial) and type-2 (schistosomal) pulmonary granulomatous inflammation in mice. 1174 43

Tuberculosis is the most prevalent infectious disease and causes more deaths than any other, yet only 5%-10% of people infected by the causative agent, Mycobacterium tuberculosis, will develop the disease. Thus, natural resistance among humans is the norm. Fundamental immune responses to M. tuberculosis are being elucidated, including induction of interferon regulatory factor-1 (IRF-1). Moreover, IRF-1 has been found necessary for normal resistance to infection by mycobacteria in mice. Roles for IRF-1 in a plethora of immune system functions have been described. This review considers molecular responses to infection by M. tuberculosis that might account for induction of IRF-1 and highlights putative connections between immunomodulatory functions of IRF-1 and immune responses relevant to infection by M. tuberculosis. However, the complexity inherent in pleiotropy and redundancy limits the ability to draw firm conclusions. In many cases, it remains to be demonstrated that a particular function of IRF-1 is the basis for a known response to infection. For example, although IRF-1 is required for a Th1 cell-mediated, adaptive immune response in some circumstances, it is not known if the Th1 response to infection by M. tuberculosis requires IRF-1. Conversely, some known contributions by IRF-1 to fundamental aspects of the immune system are not yet proven relevant in the host response to infection. For example, it is not known if control of T cell subset development by IRF-1 is significant for host defense against M. tuberculosis. Functions of other IRF that overlap with or are distinct from the functions of IRF-1 also could be important for the immune response to M. tuberculosis.
J Interferon Cytokine Res 2002 Jan
PMID:IRF and tuberculosis. 1184 72

CXC chemokine-interleukin-8 (IL-8) (CXCL-8) is a potent proinflammatory chemotactic factor that induces important immune responses for antimycobacterial defenses. However, little is known about the biochemical mechanisms by which the mycobacterial antigens upregulate the release of CXCL-8 from human monocytes. In this study, the mechanisms through which Mycobacterium bovis BCG induces CXCL-8 secretion in human monocytes were investigated. We found that M. bovis BCG induced the production of high levels of CXCL-8 by human monocytes. M. bovis-induced CXCL-8 secretion was unaffected by the protein kinase C (PKC) inhibitor bisindolylmaleimide. In contrast, preincubation of the monocytes with the protein tyrosine kinase (PTK) inhibitor genistein resulted in dose-dependent suppression of mycobacteria-induced CXCL-8 secretion. These results were further supported by the fact that treatment of monocytes with herbimycin-A, another well-described inhibitor of PTK activity with a different mechanism of action, significantly diminished the effect of M. bovis on CXCL-8 secretion. In addition, the specificity of this inhibition was demonstrated by the inability of herbimycin-A to block in a significant manner IL-1 beta induction of CXCL-8. Herbimycin-A significantly blocked tyrosine phosphorylation of p59(hck) in response to M. bovis. Finally, two specific NF-kappa B inhibitors, sulfasalazine and caffeic acid phenetyl ester (CAPE), strongly inhibited the production of CXCL-8 by human monocytes infected with M. bovis. These results show intracellular signaling pathways and a transcription factor involved in the M. bovis-mediated upregulation of CXCL-8 biosynthesis and release by human monocytes.
J Interferon Cytokine Res 2002 Feb
PMID:Signals involved in mycobacteria-induced CXCL-8 production by human monocytes. 1191 1

Activation of macrophages and other immune components to release a series of proinflammatory cytokines is one of the first events in innate resistance to intracellular infections. Severe manifestations of tuberculosis (TB) could be caused by alterations in the balance of these cytokines. In this study, lymphokine-activated killer (LAK) cells of TB patients and normal individuals were generated by stimulation with cytokines in vitro. The LAK cells of both groups were further triggered with allogeneic tumor targets. Cytokines interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were estimated in the supernatants generated in the two groups. The aim was to see if infection with TB influenced the secretory capacity of the immune cells in vitro. Reduced cytokine profiles were observed in TB patients, indicating defective interactions between patient effector cells with allogeneic transformed cells compared with normal individuals. Partial restoration of IFN-gamma production was seen with a combination of cytokines interleukin-2 (IL-2) and IL-12 in TB patients. Based on the in vitro observations, we hypothesize that in vivo also there is diminished immune cell activation of effector cells in response to the presence of infected macrophages. This probably leads to a diminished secretory function that can be corrected by the use of such cytokines as IL-2 and IL-12. The effector populations of TB patients are probably in a state of target-induced anergy, allowing the bacteria to thrive, and immunomodulatory cytokines that improve the host immune response toward countering mycobacterial infection.
J Interferon Cytokine Res 2002 Jun
PMID:Reduced cytokine secretions by LAK cells of pulmonary tuberculosis patients in response to tumor targets in vitro. 1216 71


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