Mice deficient in IL-1β-converting enzyme are defective in production of mature IL-1β and resistant to endotoxic shock

  title={Mice deficient in IL-1$\beta$-converting enzyme are defective in production of mature IL-1$\beta$ and resistant to endotoxic shock},
  author={Ping Li and Hamish Allen and Subhashish Banerjee and S Franklin and Linda Herzog and Cynthia G. Johnston and Jack McDowell and Michael Paskind and Laura Rodman and Jochen G. Salfeld and Elizabeth Towne and Daniel Edward Tracey and Scott D. Wardwell and Feng Wei and Winnie W. Wong and Robert I. Kamen and Tara Seshadri},

Figures and Tables from this paper

Characterization of mice deficient in interleukin‐1β converting enzyme

To address the biological functions of ICE, ICE‐deficient mice were generated through gene targeting technology and were resistant to LPS‐induced endotoxic shock and had impaired IL‐1α production on LPS stimulation in vitro and in vivo.

Mice Deficient in Interleukin-1β Converting Enzyme

The crystal structure of ICE reveals that the active enzyme is composed of two 20-k Da and two 10-kDa subunits to form a tetramer (7,8), and this structure is similar to that of a Tournaisian tetramer.

Interleukin-1β-converting enzyme-deficient mice resist central but not systemic endotoxin-induced anorexia.

It is demonstrated that intracerebroventricular injections of lipopolysaccharide (LPS) produced a greater reduction in both food intake and food-motivated behavior in wild-type mice compared with ICE-deficient (ICE -/-) mice.

Mice Deficient in Interleukin-1 Converting Enzyme are Resistant to Neonatal Hypoxic-Ischemic Brain Damage

Results show that ICE activity contributes to the progression of neonatal HI brain injury in this model, and whether these deleterious effects are mediated by proinflammatory actions of IL-lβ and/or by pro-apoptotic mechanisms is an important question for future studies.

Interleukin 18 Restores Defective Th1 Immunity to Candida albicans in Caspase 1-Deficient Mice

It is concluded that, while caspase 1 is not indispensable for release of mature IL-1β in candidiasis, the casp enzyme 1-dependent production of IL-18 may represent an important and novel pathway for the expression of sustained Th1 reactivity to the fungus.

Production of Mice Deficient in Genes for Interleukin (IL)-1α, IL-1β, IL-1α/β, and IL-1 Receptor Antagonist Shows that IL-1β Is Crucial in Turpentine-induced Fever Development and Glucocorticoid Secretion

IL-1β but not IL-1α is crucial in febrile and neuro-immuno-endocrine responses, and that this is because IL- 1α expression in the brain is dependent on IL-2β, as well as in peritoneal macrophages stimulated with lipopolysaccharide in vitro.

Functional role of interleukin 1 beta (IL-1 beta) in IL-1 beta- converting enzyme-mediated apoptosis

It is demonstrated that pro-IL-1 beta is a substrate of ICE relevant to cell death, and depending on the temporal cellular commitment to apoptosis, mature IL-1beta may function as a positive or negative mediator of cell death.

Interleukin-18 Regulation of Interferon γ Production and Cell Proliferation as Shown in Interleukin-1β–Converting Enzyme (Caspase-1)-Deficient Mice

The results show that IL-18 is an IL-12–independent regulator of IFNγ production and of cell proliferation induced by microbial stimuli, however, ICE-dependent processing of IL- 18 is not needed for response to mitogens or antigens.

Role of Interleukin-1β Converting Enzyme (ICE) in Acute Myelogenous Leukemia Cell Proliferation and Programmed Cell Death

Recent data indicate that ICE is a member of an increasingly recognized family of cysteine proteases, in which IL-1b˜ acts as an autocrine growth factor, or induce apoptosis.

Impaired IL-18 processing protects caspase-1-deficient mice from ischemic acute renal failure.

We sought to determine whether mice deficient in the proinflammatory caspase-1, which cleaves precursors of IL-1 beta and IL-18, were protected against ischemic acute renal failure (ARF).



Interleukin 1 beta (IL-1 beta) processing in murine macrophages requires a structurally conserved homologue of human IL-1 beta converting enzyme.

  • S. MolineauxF. Casano T. Yamin
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1993
The striking similarities of the human and murine enzymes will make it possible to assess the therapeutic potential of hICE inhibitors in murine models of disease.

Generation and analysis of interleukin-4 deficient mice.

Some but not all of the in vitro properties of IL-4 are critical for the physiology of the immune system in vivo, but the serum levels of IgG1 and IgE are strongly reduced.

Interleukin-1 and interleukin-1 antagonism.

The recent cloning of a naturally occurring IL-1 receptor antagonist (IL-1ra) has opened new experimental and clinical approaches and reduced the severity of diseases such as hemodynamic shock, lethal sepsis, inflammatory bowel disease, experimental arthritis, and the spontaneous proliferation of human leukemic cells.

A novel heterodimeric cysteine protease is required for interleukin-1βprocessing in monocytes

Purification and cloning of the complementary DNA indicates that IL-lβ-converting enzyme is composed of two nonidentical subunits that are derived from a single proenzyme, possibly by autoproteolysis.

Development and function of T cells in mice rendered interleukin-2 deficient by gene targeting

It is found that mice homozygous for the IL-2 gene mutation are normal with regard to thymocyte and peripheral T-cell subset composition, but that a dysregulation of the immune system is manifested by reduced polyclonal in vitro T- cell responses and by dramatic changes in the isotype levels of serum immunoglobulins.

Interleukin 1 is processed and released during apoptosis.

The findings suggest that cell injury is an important physiologic stimulus for release of IL-1, and the nature of the injury profoundly affects the forms ofIL-1 that are released.

IL-1 beta-converting enzyme is present in monocytic cells as an inactive 45-kDa precursor.

The inability to identify active ICE in stimulated monocytic cells was probably a reflection of the very low levels of active ICE present.

Identification of a monocyte specific pre-interleukin 1 beta convertase activity.

It is concluded that a protease activity found only in monocytes will specifically process IL-1 beta to an active form.

A recombinant human receptor antagonist to interleukin 1 improves survival after lethal endotoxemia in mice

These experiments provide direct evidence that the lethal effects of LPS may be mediated through the action of IL-1 and that theIL-1ra can provide a new treatment strategy for disease processes mediated via this cytokine.