Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023241 (Legionella)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytokine production in macrophages infected by bacteria is critical for the course of infection. However, it is not known how infection of macrophages with opportunistic bacteria leads to cytokine production in different populations of cells. Since it is possible that cytokine genes may be differentially regulated by attachment rather than by active infection, the levels of various cytokine mRNAs were measured in alveolar macrophages (AMs), peritoneal resident macrophages (RMs), and peritoneally elicited macrophages (EMs) interacting with Legionella pneumophila by using cytochalasin D-treated macrophages and a newly developed quantitative reverse transcription-PCR procedure with high-performance liquid chromatographic analysis to determine cytokine mRNA formation. Increased levels of interleukin-1 beta (IL-1 beta), IL-6, tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor, and macrophage inflammatory protein 2 mRNAs were quantitated in the macrophages responding to L. pneumophila attachment in vitro. Using this technique, we showed that the three different macrophage populations responded differently to bacterial attachment. We found that the levels of IL-6 and granulocyte-macrophage colony-stimulating factor mRNAs induced by the attachment of L. pneumophila to AMs were significantly lower than the levels in RMs but similar to the levels in EMs. Furthermore, the levels of MIP-2 mRNA in the AMs were found to be higher than those in the RMs, but similar levels were found in EMs. IL-1 beta mRNA levels were higher in both AMs and RMs than in EMs, but tumor necrosis factor alpha levels were not different among the three macrophage populations examined. Thus, the responses of macrophages to bacterial attachment in terms of cytokine mRNA levels were readily quantitated by the reverse transcription-PCR assay. However, the results obtained showed different levels of responsiveness of distinct macrophage populations to L. pneumophila attachment, and this could be related to the characteristic nature of the macrophage type examined.
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PMID:Quantitative reverse transcription-PCR analysis of Legionella pneumophila-induced cytokine mRNA in different macrophage populations by high-performance liquid chromatography. 771 7

The differentiation of HL-60, a human leukemic cell line, into monocyte-like cells (D3-HL-60 cells) is induced by 1,25-dihydroxyvitamin D3 (D3). We examined the effects of interferon (IFN) treatment of D3-HL-60 cells on the expression of cell surface antigens, the phagocytic activity for fluorescent beads, production of oxygen radicals, and intracellular growth of Legionella pneumophila. Activation of D3-HL-60 cells with IFN-gamma, Beta, and alpha for 24 h significantly increased expression of CD16, CD36, CD71, and HLA-DR antigens. IFN-gamma markedly enhanced the phagocytic activity of beads in D3-HL-60 cells. There was no significant difference in phagocytic activity between cells exposed to IFN-alpha or beta and untreated D3-HL-60 cells. IFN-alpha, beta, and gamma enhanced production of oxygen radicals, including superoxide, by D3-HL-60 cells. Superoxide production was enhanced to the greatest degree by IFN-gamma, followed by IFN-beta and then IFN-gamma. Intracellular growth of L. pneumophila in D3-HL-60 cells was inhibited by interferons (IFN-gamma > beta > gamma). Similar results were obtained in human mononuclear cells. These data indicate that interferons can act as biologic response modifiers not only in human mononuclear cells but also in differentiated leukemic cells. Our results may have implications for the development of differentiation therapy for treatment of leukemia.
J Interferon Cytokine Res 1996 May
PMID:Effects of interferon-alpha, beta, and gamma on the function of differentiated leukemic HL-60 cells induced by 1,25-dihydroxyvitamin D3. 872 74

Alveolar macrophages are the preferential site for growth of Legionella pneumophila (Lp) during infection. However, the study of Lp infection in alveolar macrophages is difficult due to the limitation of available primary alveolar macrophages. In the present study, we established an in vitro Lp infection model in alveolar macrophages using a continuous cell line of murine alveolar macrophages designated MH-S. Infection of both MH-S cells and primary mouse alveolar macrophages obtained by alveolar lavage with virulent L. pneumophila (Lp-V) showed vigorous growth of the bacteria, but infection with avirulent L. pneumophila (Lp-Av) resulted in only minimum growth. Cytokine message expression determination in the MH-S cells after infection showed strong induction of interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha messages induced by Lp-V but minimal induction of these cytokines by Lp-Av infection. IL-1 alpha protein secretion and the message levels for IL-1 alpha were also analyzed, and remarkable induction of IL-1 alpha was evident in both macrophage types when infected with Lp-V. Analysis of IL-12 p40 responses of both macrophage types to Lp-V infection assessed by reverse transcriptase/polymerase chain reaction revealed induction of increased message levels, but significant levels were induced only slowly. Determination of IL-12 protein secretion by enzyme-linked immunosorbent assay of culture supernatants from both macrophage types infected with either Lp-V or Lp-Av showed only minimum production. Thus, MH-S alveolar macrophages showed a similar response to Lp infection compared with primary alveolar macrophages and can be a useful in vitro model system to study Lp infection. The study also revealed the restricted IL-12 protein secretion of alveolar macrophages by Lp infection.
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PMID:Alveolar macrophage cell line MH-S is valuable as an in vitro model for Legionella pneumophila infection. 1124 32

Delta-9-tetrahydrocannabinol (THC) injection suppresses serum interleukin-12 (IL-12) levels in Legionella pneumophila-infected mice. Dendritic cells are a major producer of IL-12 and mouse, bone marrow-derived dendritic cell cultures produced high levels of the IL-12p40 following L. pneumophila infection. Treatment with THC suppressed this cytokine response in a concentration-dependent manner and the endocannabinoid, 2-arachidonoyolglycerol, less potently suppressed cytokine production. Dendritic cells expressed mRNA for cannabinoid receptor 1 (CB(1)), cannabinoid CB(2) receptor, and vanilloid receptor 1 (TRPV1) and the addition of the G(i) inhibitor, pertussis toxin, completely attenuated suppression induced by 3 and 6 muM THC but not by 10 muM THC. Furthermore, THC suppression was partially attenuated in dendritic cells from cannabinoid CB(1) receptor and CB(2) receptor knockout mice and in dendritic cells co-treated with THC and cannabinoid receptor antagonists. Cytokine suppression was not attenuated by pretreatment with the TRPV1 antagonist, capsazepine. These results suggest that THC-induced suppression of serum IL-12 is partly due to a suppression of IL-12 production by dendritic cells and that G(i) signaling and cannabinoid receptors, but not TRPV1, are involved in this suppressive effect.
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PMID:Role of cannabinoid receptors in Delta-9-tetrahydrocannabinol suppression of IL-12p40 in mouse bone marrow-derived dendritic cells infected with Legionella pneumophila. 1644 17

Legionella pneumophila is one of the most important pathogens which cause community-acquired pneumonia. Although TNF-alpha is considered to play an important role in response to bacteria, the role of the TNF-alpha receptor on L. pneumophila infection remains to be elucidated. To investigate this, we infected TNF receptor deficient mice with L. pneumophila. L. pneumophila was inoculated intranasally into TNF receptor (TNFR)-1-knock-out mice or TNFR2-knock-out mice. The mortality rate, histology of the lung, bacterial growth in the lung, and bronchoalveolar lavage (BAL) fluids were investigated. The bacterial growth of L. pneumophila in the macrophages was also studied. Almost all the mice survived after an intranasal inoculation of 1x10(6)CFU/head of L. pneumophila, but more than 90% mice were killed after inoculation of 1x10(8)CFU/head of L. pneumophila. In the case of TNFR1-knock-out mice and TNFR2-knock-out mice, a high mortality rate was observed after inoculation of 1x10(7)CFU/head of L. pneumophila in comparison to wild-type mice. The lung histology from both the TNFR1-knock-out mice documented severe lung injury at day 3 after inoculation. The clearance of L. pneumophila in the lung of the TNFR1-knock-out mice was slower than those from both the TNFR2-knock-out mice and the wild-type mice. Moreover, L. pneumophila growth in the peritoneal macrophages from the TNFR1-knock-out mice was observed. Interestingly, a lack of neutrophils accumulation in the BAL fluids and a dysregulation of cytokines (IFN-gamma, interleukin-12, and TNF-alpha) were observed in the TNFR1-knock-out mice. On the contrary, large accumulation of neutrophils in BAL fluids was observed in TNFR2-knock-out mice. These data suggested that a TNFR1 deficiency led to a compromise of the innate immunity against L. pneumophila, while a TNFR2 deficiency induced an excessive inflammatory response and resulted in death. The present study confirmed that TNFR1 and TNFR2 play a crucial, but different role in the control of L. pneumophila-induced mortality.
Cytokine 2008 Nov
PMID:TNF receptor 1 and 2 contribute in different ways to resistance to Legionella pneumophila-induced mortality in mice. 1883 75