Tumor necrosis factor alpha, interleukin-1 alpha, interleukin-6, and prostaglandin E2 production in murine peritoneal macrophages infected with Ehrlichia risticii

Heeckeren, Anna M. van; Rikihisa, Yasuko; Park, J; Fertel, Richard H.

doi:10.1128/iai.61.10.4333-4337.1993

Cited by 25 publications

(13 citation statements)

References 24 publications

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“…This explains the very small amounts of TNF-a present during persistent infection of peritoneal macrophages by E. risticii in comparison with the amount of TNF-ca secreted by the same macrophages triggered by purified LPS only. This is also in agreement with the fact that E. risticii infection of macrophages inhibited the release of TNF-oa triggered by a further action of the endotoxin (27). Our data, which showed a bactericidal effect on B. suis 503 of macrophages activated by exogenous TNF-ot, strongly suggested that any defect in TNF-ot production by Brucellainfected mononuclear phagocytes was a direct consequence of Brucella virulence.…”

Section: Discussionsupporting

confidence: 91%

“…Moreover, we also noticed that in differentiated U937 cells, adenosine promoted an increase in cyclic AMP, a second messenger known to negatively affect TNF-a production. An increase in cyclic AMP has been reported in macrophages infected by Ehrlichia risticii (27). Thus, adenosine could be the factor or one of them which negatively regulates TNF-a production.…”

Section: Discussionmentioning

confidence: 97%

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Live Brucella spp. fail to induce tumor necrosis factor alpha excretion upon infection of U937-derived phagocytes

et al. 1994

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Tumor necrosis factor alpha (TNF-a) plays a central role in activation of first-line defenses of a host against foreign organisms. To determine whether Bruceila infection modulated TNF-aL production, we measured the biological activity of this cytokine in supernatants of U937 cell-derived macrophages and of fresh human monocytes infected with Brucella spp. Neither the smooth nor rough Bruceila strains used induced any measurable TNF-a excretion upon infection. On the contrary, as reported before for other gram-negative bacteria, phagocytosis of nonpathogenic Escherichia coli was followed by a rapid and transient induction of TNF-a release, suggesting an involvement of this cytokine in some autocrine process. As expected, the Brucella strains tested survived and/or multiplied within U937-derived macrophages, whereas E. coli was rapidly eliminated after phagocytosis. Immunoglobulin G opsonization of E. coli strains enhanced their intracellular killing and strongly potentiated TNF-a secretion. Immunoglobulin G opsonization of Bruceila strains, in contrast, did not lead to TNF-a production, although their rate of intracellular multiplication was reduced. Killed brucellae, however, promoted a significant excretion of TNF-at from U937-derived macrophages into cell culture supernatants. We finally demonstrated that pretreatment of U937-derived macrophages with exogenous TNF-a significantly inhibited intracellular multiplication of Brucella spp. These results and experiments performed on fresh human monocytes or with isolated lipopolysaccharide (LPS) showed that (i) differences in

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 97%

Live Brucella spp. fail to induce tumor necrosis factor alpha excretion upon infection of U937-derived phagocytes

et al. 1994

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“…Elevated PKA activity in THP-1 cells infected with E. chaffeensis serves as a mechanism for inhibition of tyrosine phosphorylation. E. risticii infection causes a significant increase in cytoplasmic cAMP levels in the colonic mucosa of horses (28) and in mouse peritoneal macrophages (34). Recent studies suggest that 8-bromo-cAMP inhibits Stat1 activation in human FIG.…”

Section: Ifn-␥ Induces Tyrosine Phosphorylation Of Stat1 Jak1 Andmentioning

confidence: 99%

Protein Kinase A-Mediated Inhibition of Gamma Interferon-Induced Tyrosine Phosphorylation of Janus Kinases and Latent Cytoplasmic Transcription Factors in Human Monocytes byEhrlichia chaffeensis

Lee

Rikihisa

1998

Infect Immun

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Ehrlichia chaffeensis, an obligatory intracellular bacterium of monocytes or macrophages, is the etiologic agent of human monocytic ehrlichiosis. Our previous study showed that gamma interferon (IFN-γ) added prior to or at early stage of infection inhibited infection of human monocytes with E. chaffeensis; however, after 24 h of infection, IFN-γ had no antiehrlichial effect. To test whether ehrlichial infection disrupts Janus kinase (Jak) and signal transducer and activator of transcription (Stat) signaling induced by IFN-γ, tyrosine phosphorylation of Stat1, Jak1, and Jak2 in E. chaffeensis-infected THP-1 cells was examined by immunoprecipitation followed by immunoblot analysis. Viable E. chaffeensis organisms blocked tyrosine phosphorylation of Stat1, Jak1, and Jak2 in response to IFN-γ within 30 min of infection. Similar results were obtained with human peripheral blood monocytes infected with E. chaffeensis. Heat or proteinase K treatment but not periodate treatment of E. chaffeensisabrogated the inhibitory effect, suggesting that protein factor(s) ofE. chaffeensis is responsible for the inhibition of IFN-γ-induced tyrosine phosphorylation. Preincubation ofE. chaffeensis with the Fab fragment of dog anti-E. chaffeensis immunoglobulin G also abrogated the inhibitory effect. On the other hand, monodansylcadaverine, which does not block binding but blocks internalization of ehrlichiae into macrophages, did not have any influence on the tyrosine phosphorylation. These results indicate that ehrlichial binding to host cells is sufficient to inhibit Stat1 tyrosine phosphorylation induced by IFN-γ. Protein kinase A (PKA) activity in THP-1 cells increased approximately 25-fold within 30 min of infection with E. chaffeensis. In THP-1 cells pretreated with a PKA inhibitor, Rp isomer of adenosine 3′,5′-cyclic phosphorothioate, E. chaffeensis-induced inhibition of Stat1 tyrosine phosphorylation was partially abrogated. These results suggest thatE. chaffeensis blocks IFN-γ-induced tyrosine phosphorylation of Jak and Stat through raising PKA activity in THP-1 cells, which may be an important survival mechanism of ehrlichiae within the host cell.

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“…The sustained NF-B activation may play a role in the induction of major proinflammatory cytokines by anti-E. chaffeensis antibody and E. chaffeensis. We previously showed that E. risticii organisms induced significantly lower levels of IL-6, TNF-␣, and prostaglandin E 2 in mouse peritoneal macrophages than Escherichia coli LPS induces (38). We also showed that IL-1␤, IL-8, and IL-10 but not TNF-␣ and IL-6 are induced in human monocytes and THP-1 cells infected with E. chaffeensis (22).…”

Section: Discussionmentioning

confidence: 78%

Anti-Ehrlichia chaffeensis antibody complexed with E. chaffeensis induces potent proinflammatory cytokine mRNA expression in human monocytes through sustained reduction of IkappaB-alpha and activation of NF-kappaB

Lee

Rikihisa

1997

Infect Immun

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Ehrlichia chaffeensis is an obligatory intracellular bacterium that infects monocytes and macrophages and is the etiologic agent of human ehrlichiosis in the United States. Our previous studies showed that the exposure of human monocytes to E. chaffeensis induces the expression of interleukin-1␤ (IL-1␤), IL-8, and IL-10 genes in vitro but not the expression of tumor necrosis factor alpha (TNF-␣) and IL-6 mRNAs. In this study, the effect of anti-E. chaffeensis antibody complexed with E. chaffeensis on the expression of major proinflammatory cytokines in human monocytes was examined. Human monocytic cell line THP-1 was treated with E. chaffeensis which had been preincubated with human anti-E. chaffeensis serum for 2 h, and the levels of cytokine mRNAs were evaluated by competitive reverse transcription-PCR. Anti-E. chaffeensis antibody complexed with E. chaffeensis significantly enhanced mRNA expression of IL-1␤ in THP-1 cells. The expression of TNF-␣ and IL-6 mRNAs was also induced. The levels of secreted IL-1␤, TNF-␣, and IL-6 during 24 h of stimulation were comparable to those induced by Escherichia coli lipopolysaccharide at 1 g/ml. Fab fragment of anti-E. chaffeensis immunoglobulin G complexed with E. chaffeensis did not induce any of these three cytokines, indicating that ehrlichial binding is required for IL-1␤ mRNA expression and that binding of the immune complex to the Fc␥ receptor is required for TNF-␣ and IL-6 mRNA expression and enhanced IL-1␤ mRNA expression. Furthermore, prolonged degradation of IB-␣ and activation of NF-B were demonstrated in THP-1 cells exposed to anti-E. chaffeensis serum and E. chaffeensis. This result implies that development of anti-E. chaffeensis antibody in patients can result in the production of major proinflammatory cytokines, which may play an important role in the pathophysiology of ehrlichiosis and immune responses to it.

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Tumor necrosis factor alpha, interleukin-1 alpha, interleukin-6, and prostaglandin E2 production in murine peritoneal macrophages infected with Ehrlichia risticii

Cited by 25 publications

References 24 publications

Live Brucella spp. fail to induce tumor necrosis factor alpha excretion upon infection of U937-derived phagocytes

Live Brucella spp. fail to induce tumor necrosis factor alpha excretion upon infection of U937-derived phagocytes

Protein Kinase A-Mediated Inhibition of Gamma Interferon-Induced Tyrosine Phosphorylation of Janus Kinases and Latent Cytoplasmic Transcription Factors in Human Monocytes byEhrlichia chaffeensis

Anti-Ehrlichia chaffeensis antibody complexed with E. chaffeensis induces potent proinflammatory cytokine mRNA expression in human monocytes through sustained reduction of IkappaB-alpha and activation of NF-kappaB

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