Caspase 1-independent IL-1β release and inflammation induced by the apoptosis inducer Fas ligand

Miwa, Keiko; Asano, Masahide; Horai, Reiko; Iwakura, Yoichiro; Nagata, Shinji; Suda, Takafumi

doi:10.1038/3276

Cited by 366 publications

(302 citation statements)

References 40 publications

Supporting

Mentioning

275

Contrasting

Unclassified

Order By: Relevance

“…53 Although caspase-1 has greater specificity for pro-IL-18, other caspases, that is, caspase-3-like proteases, are able to process pro-IL-1b and pro-IL-18 in response to antigenic stimulation or FasL, providing an alternative pathway for cytokine generation. [53][54][55] Consistent with the above reports, we demonstrated the release of IL-18 and IFN-g in response to ConA-induced hepatitis. In addition to inhibiting apoptosis in the liver, mice transduced with CrmA inhibited IFN-g and IL-18 production induced by ConA (Figure 6).…”

Section: Discussionsupporting

confidence: 89%

CrmA gene expression protects mice against concanavalin-A-induced hepatitis by inhibiting IL-18 secretion and hepatocyte apoptosis

et al. 2003

View full text Add to dashboard Cite

Activated cytotoxic T-cell-mediated hepatocyte apoptosis via Fas/Fas-ligand and perforin/granzyme pathways are believed to involve the model of concanavalin A (ConA)-induced hepatitis. The purpose of the present study is to investigate whether the cytokine response modifier A (crmA) gene effectively inhibits the hepatocyte apoptosis of ConAinduced hepatitis. We examined survival rates, liver pathology, immune histological changes, and cytokine profiles from mice receiving the recombinant adenovirus vectors containing cre and/or crmA genes, transferred to the liver 3 days before ConA injection, and a crmA gene nonexpression control group. Injection of ConA into mice rapidly led to massive hepatocyte apoptosis, and infiltration of leukocytes, especially CD11b + inflammatory cells. In contrast, liver damage was dramatically reduced in the mice that expressed the crmA gene. However, infiltration by CD4 + cells was not affected. The survival of the mice increased significantly to 100% in the treated group versus the control group. Furthermore, we demonstrated that interleukin (IL)-18 plays an important role in ConA-induced hepatitis, and that crmA expression significantly inhibited IL-18 secretion. Our results showed that the crmA gene effectively inhibits apoptosis induced by ConA hepatitis. This indicates a potential therapeutic usage of crmA for protection from cellular damage due to hepatitis.

show abstract

Section: Discussionsupporting

confidence: 89%

CrmA gene expression protects mice against concanavalin-A-induced hepatitis by inhibiting IL-18 secretion and hepatocyte apoptosis

et al. 2003

View full text Add to dashboard Cite

show abstract

“…Although more studies are needed, the recruitment of neutrophils might be due to the chemotactic effect of FasL. 45,46 In summary, we constructed a bioactive adenoviral vector expressed murine FasL in vitro. In a murine model of OVA-induced asthma, the pulmonary expression of adenoviral vector expressing FasL before the airway challenge could significantly alleviated the development of AHR, reduced the infiltration of eosinophils and lymphocytes, and decreased eosinophil chemoattractant eotaxin, proinflammatory cytokines KC, and TNF-a production, and Th2 cytokines IL-5 and IL-13 production.…”

Section: Discussionmentioning

confidence: 99%

Adenovirus expressing Fas ligand gene decreases airway hyper-responsiveness and eosinophilia in a murine model of asthma

Chuang¹,

Cl²,

et al. 2004

Gene Ther

View full text Add to dashboard Cite

Allergic asthma is characterized by airway hyper-responsiveness (AHR) and cellular infiltration of the airway with predominantly eosinophils and Th2 cells. The normal resolution of inflammation in the lung occurs through the regulated removal of unneeded cells by Fas-Fas ligandmediated apoptosis. Fas ligand (FasL) is a member of the tumor necrosis factor family, and when bound to Fas, it induces apoptosis of the cells. To examine the effect of the FasL gene on airway inflammation and immune effector cells in allergic asthma, recombinant adenovirus expressing murine FasL (Ad-FasL) was delivered intratracheally into ovalbumin (OVA)-immunized mice. We found that a single administration of Ad-FasL in OVA-immunized mice significantly alleviated AHR and eosinophilia by inducing the apoptosis of eosinophils and/or reducing eosinophil attractant factors, such as IL-5 and eotaxin levels. The number of infiltrated lymphocytes and Th2 cytokines, including IL-5 and IL-13, decreased in OVA-immunized mice by administration of Ad-FasL. KC and TNF-a production also decreased in AdFasL-treated OVA-immunized mice. These findings indicated that the administration of Ad-FasL to OVA-sensitized mice significantly suppressed pulmonary allergic responses. Although more studies are needed, these results suggested that Ad-FasL might be applied as an alternative therapy for allergic asthma.

show abstract

“…A possible mechanism is that CD95L acts on surrounding cells to induce the production of granulocyte chemoattractants. It has been reported that CD95L induces the processing and release of IL-1 g , which may be responsible for the infiltration by neutrophils [41]. CD95L may act on resident macrophages leading to increased production of IL-1 g and macrophage inflammatory proteins [42].…”

Section: Discussionmentioning

confidence: 99%

The influence of CD95L expression on tumor rejection in mice

Igney¹,

Behrens²,

Krammer³

2003

Eur J Immunol

View full text Add to dashboard Cite

Many tumors express the death ligand CD95L (CD178, APO-1L, FasL) and can kill activated T cells in vitro. This may enable the tumor cells to suppress anti-tumor immune responses, a phenomenon called "tumor counterattack". Preliminary evidence of tumor counterattack in human tumors exists. However, CD95L-expressing tumors are rapidly rejected in mice. In order to clarify this controversial situation we investigated whether the level or the time point of CD95L expression might be critical factors determining tumor counterattack versus tumor rejection. We generated CD95-resistant tumor cell lines expressing different levels of CD95L (LKC-CD95L). In nude mice the CD95L expression level had no influence on the growth of the CD95L + tumors. In contrast, a CD95L -control tumor cell line (LKC) grew much faster. In addition, we generated a CD95-resistant cell line in which CD95L was induced via the tet system (LKCR-tetCD95L). Induction of CD95L in established tumors in nude and NOD/SCID mice led to rapid rejection of the tumors. Induction of lower CD95L expression levels delayed tumor rejection only marginally. These results demonstrate that rejection of CD95L-expressing tumors in mice is not a result of overexpression and does not depend on the presence of CD95L at the onset of tumor progression.

show abstract

Caspase 1-independent IL-1β release and inflammation induced by the apoptosis inducer Fas ligand

Cited by 366 publications

References 40 publications

CrmA gene expression protects mice against concanavalin-A-induced hepatitis by inhibiting IL-18 secretion and hepatocyte apoptosis

CrmA gene expression protects mice against concanavalin-A-induced hepatitis by inhibiting IL-18 secretion and hepatocyte apoptosis

Adenovirus expressing Fas ligand gene decreases airway hyper-responsiveness and eosinophilia in a murine model of asthma

The influence of CD95L expression on tumor rejection in mice

Contact Info

Product

Resources

About