Fas (CD95) induces macrophage proinflammatory chemokine production via a MyD88-dependent, caspase-independent pathway

Altemeier, William A.; Zhu, Xiaodong; Berrington, William R.; Harlan, John M.; Liles, W. Conrad

doi:10.1189/jlb.1006652

Cited by 39 publications

(38 citation statements)

References 43 publications

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“…Yet, whereas CD95L treatment induced efficient recruitment of FADD to CD95 in the CD95 apoptosis sensitive thymoma E20 cells, recruitment of FADD to CD95 could not be detected in stimulated primary macrophages ( Figure S2). Consistently, macrophages are resistant to CD95-induced cell death (Altemeier et al, 2007;Park et al, 2003;Shimizu et al, 2005). There is increasing evidence that CD95L is involved in processes other than apoptosis (Sancho-Martinez and Martin-Villalba, 2009).…”

Section: Cd95l Induces Activation Of Pi3k and Metalloproteinases Via mentioning

confidence: 94%

CD95-Ligand on Peripheral Myeloid Cells Activates Syk Kinase to Trigger Their Recruitment to the Inflammatory Site

et al. 2010

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Injury to the central nervous system initiates an uncontrolled inflammatory response that results in both tissue repair and destruction. Here, we showed that, in rodents and humans, injury to the spinal cord triggered surface expression of CD95 ligand (CD95L, FasL) on peripheral blood myeloid cells. CD95L stimulation of CD95 on these cells activated phosphoinositide 3-kinase (PI3K) and metalloproteinase-9 (MMP-9) via recruitment and activation of Syk kinase, ultimately leading to increased migration. Exclusive CD95L deletion in myeloid cells greatly decreased the number of neutrophils and macrophages infiltrating the injured spinal cord or the inflamed peritoneum after thioglycollate injection. Importantly, deletion of myeloid CD95L, but not of CD95 on neural cells, led to functional recovery of spinal injured animals. Our results indicate that CD95L acts on peripheral myeloid cells to induce tissue damage. Thus, neutralization of CD95L should be considered as a means to create a controlled beneficial inflammatory response.

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Section: Cd95l Induces Activation Of Pi3k and Metalloproteinases Via mentioning

confidence: 94%

CD95-Ligand on Peripheral Myeloid Cells Activates Syk Kinase to Trigger Their Recruitment to the Inflammatory Site

et al. 2010

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“…In addition, Miwa et al (3) and our group have shown that innate inflammatory cytokines such as IL-18 and IL-1b are produced from neutrophils and macrophages via Fas signaling without the induction of apoptosis (4). Furthermore, it has been shown that the production of other cytokines or chemokines is also induced by Fas stimulation (5)(6)(7)(8)(9)(10). These data indicate the possibility that Fas signaling plays important roles in the innate immune system in response to infection by pathogenic microbes; however, the precise molecular mechanisms and physiological roles of inflammatory cytokine production via Fas signaling in bacterial infection are not clear.…”

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confidence: 93%

Fas-Mediated Inflammatory Response inListeria monocytogenesInfection

Uchiyama

Yonehara

Tsutsui

2013

The Journal of Immunology

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The molecular mechanisms of Fas (CD95/Apo-1)-mediated apoptosis are increasingly understood. However, the role of Fas-mediated production of proinflammatory cytokines such as IL-18 and IL-1β in bacterial infection is unclear. We demonstrate the importance of Fas-mediated signaling in IL-18/IL-1β production postinfection with Listeria monocytogenes without the contribution of caspase-1 inflammasome. IL-18/IL-1β production in L. monocytogenes–infected peritoneal exudate cells from Fas-deficient mice was lower than those from wild type mice, indicating that Fas signaling contributes to cytokine production. L. monocytogenes infection induced Fas ligand expression on NK cells, which stimulates Fas expressed on the infected macrophages, leading to the production of IL-18/IL-1β. This was independent of caspase-1, caspase-11, and nucleotide-binding domain and leucine-rich repeat–containing receptors (NLRs) such as Nlrp3 and Nlrc4, but dependent on apoptosis-associated speck-like protein containing a caspase recruitment domain. Wild type cells exhibited caspase-8 activation, whereas Fas-deficient cells did not. L. monocytogenes–induced caspase-8 activation was abrogated by inhibitor for intracellular reactive oxygen species, N-acetyl-L-cysteine. L. monocytogenes–infected macrophages produced type-I IFNs such as IFN-β1, which was required for Il18 gene expression. Thus, Fas signaling regulates innate inflammatory cytokine production in L. monocytogenes infection.

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“…Specifically, the Fas pathway has been investigated as a potential contributor to the inflammation and alveolar epithelial cell apoptosis observed in the lungs of patients with ALI (13,14). The Fas pathway, activated by the binding of Fas ligand (FasL) to Fas on the surface of a cell, leads to an intracellular cascade resulting in inflammation and apoptosis of the Fas-bearing cell.…”

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confidence: 99%

Genetic Variation in theFASGene and Associations with Acute Lung Injury

Glavan¹,

Holden²,

Goss³

et al. 2011

Am J Respir Crit Care Med

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Rationale: Fas (CD95) modulates apoptosis and inflammation and is believed to play an important role in lung injury. Objectives: To determine if common genetic variation in FAS is associated with acute lung injury (ALI) susceptibility, risk of death, and FAS gene expression. Methods: We genotyped 14 single nucleotide polymorphisms (tagSNPS) in FAS in samples from healthy white volunteers (control subjects, n 5 294) and patients with ALI (cases, n 5 324) from the ARDSnet Fluid and Catheter Treatment Trial (FACTT). FAS genotypes associated with ALI in the discovery study were confirmed in a nested case-control validation study of critically ill patients at risk for ALI (n 5 657). We also tested for associations between selected tagSNPS and FAS mRNA levels in whole blood from healthy control subjects exposed to media alone or LPS ex vivo. and ALI case status. Haplotype-based analyses suggested that three of the tagSNPs (FAS 9325G.A , FAS 21541C.T , and FAS 24484A.T ) function as a unit. The association with this haplotype and ALI was validated in a nested case-control study of at-risk subjects (P 5 0.05). This haplotype was also associated with increased FAS mRNA levels in response to LPS stimulation. There was no association between FAS polymorphisms and risk of death among ALI cases. Conclusions: Common genetic variants in FAS are associated with ALI susceptibility. This is the first genetic evidence supporting a role for FAS in ALI.

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Fas (CD95) induces macrophage proinflammatory chemokine production via a MyD88-dependent, caspase-independent pathway

Cited by 39 publications

References 43 publications

CD95-Ligand on Peripheral Myeloid Cells Activates Syk Kinase to Trigger Their Recruitment to the Inflammatory Site

CD95-Ligand on Peripheral Myeloid Cells Activates Syk Kinase to Trigger Their Recruitment to the Inflammatory Site

Fas-Mediated Inflammatory Response inListeria monocytogenesInfection

Genetic Variation in theFASGene and Associations with Acute Lung Injury

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