Induction of the IL-10 gene via the Fas receptor in monocytes - an anti-inflammatory mechanism in the absence of apoptosis

Daigle, Isabelle; Rückert, Beate; Schnetzler, Gabriel; Simon, Hans‐Uwe

doi:10.1002/1521-4141(200010)30:10<2991::aid-immu2991>3.0.co;2-1

Cited by 23 publications

(18 citation statements)

References 29 publications

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“…It has also been demonstrated that Fas signaling in macrophages induces IL-10 gene expression. 36 We have recently reported that natural killer T cells in the liver express Fas-ligand directly through toll-like receptors induced by gram-negative bacteria such as Salmonella choleraesuis and E. coli. 37,38 Taken together, it also seems likely that Fas-expressing Kupffer cells in BDL mice are susceptible to signals via Fas-ligand expressed on natural killer T cells after E. coli infection and predominantly produce IL-10.…”

Section: Discussionmentioning

confidence: 99%

Kupffer cell-derived interleukin 10 is responsible for impaired bacterial clearance in bile duct-ligated mice

et al. 2004

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Extrahepatic cholestasis often evokes liver injury with hepatocyte apoptosis, aberrant cytokine production, and-most importantly-postoperative septic complications. To clarify the involvement of aberrant cytokine production and hepatocyte apoptosis in impaired resistance to bacterial infection in obstructive cholestasis, C57BL/6 mice or Fas-mutated lpr mice were inoculated intraperitoneally with 10 7 colony-forming units of Escherichia coli 5 days after bile duct ligation (BDL) or sham celiotomy. Cytokine levels in sera, liver, and immune cells were assessed via enzyme-linked immunosorbent assay or real-time reverse-transcriptase polymerase chain reaction. BDL mice showed delayed clearance of E. coli in peritoneal cavity, liver, and spleen. Significantly higher levels of serum interleukin (IL) 10 with lower levels of IL-12p40 were observed in BDL mice following E. coli infection. Interferon ␥ production from liver lymphocytes in BDL mice was not increased after E. coli infection either at the transcriptional or protein level. Kupffer cells from BDL mice produced low levels of IL-12p40 and high levels of IL-10 in vitro in response to lipopolysaccharide derived from E. coli. In vivo administration of anti-IL-10 monoclonal antibody ameliorated the course of E. coli infection in BDL mice. Furthermore, BDL-lpr mice did not exhibit impairment in E. coli killing in association with little hepatic injury and a small amount of IL-10 production. In conclusion, increased IL-10 and reciprocally suppressed IL-12 production by Kupffer cells are responsible for deteriorated resistance to bacterial infection in BDL mice. Fasmediated hepatocyte apoptosis in cholestasis may be involved in the predominant IL-10 production by Kupffer cells. (HEPATOLOGY 2004;40:414 -423.)

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Section: Discussionmentioning

confidence: 99%

Kupffer cell-derived interleukin 10 is responsible for impaired bacterial clearance in bile duct-ligated mice

et al. 2004

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“…Recent studies have demonstrated that the FasL can transduce signals via the Fas receptor using nonapoptotic pathways in monocytes (33), dendritic cells (34), and T cells (35). In addition, studies have shown that CD4 ϩ T cells and CD8 ϩ T cells exhibit different sensitivities to Fasmediated apoptosis (36,37).…”

Section: Discussionmentioning

confidence: 99%

Membrane Fas Ligand Activates Innate Immunity and Terminates Ocular Immune Privilege

Gregory

Repp

Holhbaum

et al. 2002

The Journal of Immunology

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It has been proposed that the constitutive expression of Fas ligand (FasL) in the eye maintains immune privilege, in part through inducing apoptosis of infiltrating Fas+ T cells. However, the role of FasL in immune privilege remains controversial due to studies that indicate FasL is both pro- and anti-inflammatory. To elucidate the mechanism(s) by which FasL regulates immune privilege, we used an ocular tumor model and examined the individual roles of the membrane-bound and soluble form of FasL in regulating ocular inflammation. Following injection into the privileged eye, tumors expressing only soluble FasL failed to trigger inflammation and grew progressively. By contrast, tumors expressing only membrane FasL 1) initiated vigorous neutrophil-mediated inflammation, 2) terminated immune privilege, and 3) were completely rejected. Moreover, the rejection coincided with activation of both innate and adaptive immunity. Interestingly, a higher threshold level of membrane FasL on tumors is required to initiate inflammation within the immune privileged eye, as compared with nonprivileged sites. The higher threshold is due to the suppressive microenvironment found within aqueous humor that blocks membrane FasL activation of neutrophils. However, aqueous humor is unable to completely block the proinflammatory effects of tumor cells that express high levels of membrane FasL. In conclusion, our data indicate that the function of FasL on intraocular tumors is determined by the microenvironment in conjunction with the form and level of FasL expressed.

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“…The finding that Fas cross-linking induces the expression of IL-10 in murine lymphoid cells (10,11) prompted us to investigate whether a similar pathway operates in Jurkat cells. The transcription of IL-10 in Jurkat cells was induced by CH-11 in a dosedependent manner (Fig.…”

Section: Enhanced Transcription Of the Il-10 Gene In Jurkat Cells Is mentioning

confidence: 99%

“…Fas-L costimulates the proliferation of CD8 ϩ T cells and resting T lymphocytes by augmenting IL-2 production (8,9). Fas-mediated transcriptional activation of the IL-10 gene in monocytes was followed by the release of large amounts of cytokines and occurred in the absence of apoptosis (10). Moreover, apoptosis in lymphoid cells upon Fas activation led to rapid production of IL-10, which is probably responsible for the induction of immune deviation during Ag presentation (11).…”

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confidence: 99%

Mediation of Enhanced Transcription of the IL-10 Gene in T Cells, Upon Contact with Human Glioma Cells, by Fas Signaling Through a Protein Kinase A-Independent Pathway

Yang

Lin

Hor

et al. 2003

The Journal of Immunology

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Elevated expression of IL-10 has been frequently observed in tumor tissues and tumor-infiltrating cells. We show herein that transcription of the IL-10 gene in primary peripheral T cells and T cell lines is up-regulated upon contact with glioma cells without an induction of apoptosis in those T cells. Glioma-associated IL-10 induction was suppressed by interrupting the engagement of Fas and its ligand (Fas-L) with the antagonistic Ab, ZB4, by reducing Fas-L expression of glioma cells using the Fas-L-specific ribozyme, or by preventing cell-to-cell contact in a Transwell culture setting. Cross-linking of Fas with the agonistic Ab, CH-11, triggered apoptosis and enhanced the expression of IL-10 in Jurkat cells at the transcriptional and translational levels. Inhibiting caspase activities by caspase inhibitors, Z-VAD (Z-Val-Ala-Asp(Ome)-fluoromethylketone) and Z-IETD (Z-Ile-Glu(Ome)-Thr(Ome)-Asp(Ome)-fluoromethylketone), abolished this IL-10 induction in Jurkat cells. Intracellular staining detected IL-10 proteins in Fas-cross-linked Jurkat cells and in PHA-activated T cells. However, few IL-10 proteins were detectable in Jurkat cells cocultured with glioma cells, indicating a requirement of other factors for IL-10 production. Direct activation of protein kinase A (PKA) by forskolin elevated the transcription of IL-10 in Jurkat cells. However, KT5720, a selective PKA inhibitor, reduced neither anti-Fas-triggered nor glioma-associated IL-10 expression. Phosphorylation of cAMP response element binding protein and activating transcription factor-1 in Jurkat cells was not affected by coculturing with glioma cells or by anti-Fas treatment, further suggesting a PKA-independent pathway. In summary, our results demonstrate nonlethal cross-talk between tumor and immune cells leading to IL-10 dysregulation in T cells, which might contribute to Fas-L+ tumor-associated immunosuppression.

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Induction of the IL-10 gene via the Fas receptor in monocytes - an anti-inflammatory mechanism in the absence of apoptosis

Cited by 23 publications

References 29 publications

Kupffer cell-derived interleukin 10 is responsible for impaired bacterial clearance in bile duct-ligated mice

Kupffer cell-derived interleukin 10 is responsible for impaired bacterial clearance in bile duct-ligated mice

Membrane Fas Ligand Activates Innate Immunity and Terminates Ocular Immune Privilege

Mediation of Enhanced Transcription of the IL-10 Gene in T Cells, Upon Contact with Human Glioma Cells, by Fas Signaling Through a Protein Kinase A-Independent Pathway

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