A Surface Amebic Cysteine Proteinase Inactivates Interleukin-18

DOI Web Site 被引用文献4件
  • Xuchu Que
    Departments of Pathology
  • Soo-Hyun Kim
    Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262
  • Mohammed Sajid
    Department of Pathology, University of California, San Francisco, California 94142
  • Lars Eckmann
    Medicine, University of California, San Diego, California 92103
  • Charles A. Dinarello
    Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262
  • James H. McKerrow
    Department of Pathology, University of California, San Francisco, California 94142
  • Sharon L. Reed
    Departments of Pathology

抄録

<jats:title>ABSTRACT</jats:title><jats:p>Amebiasis is a major cause of morbidity and mortality worldwide. Invasion by<jats:italic>Entamoeba histolytica</jats:italic>trophozoites causes secretion of proinflammatory cytokines from host epithelial cells, leading to a local acute inflammatory response, followed by lysis of colonic cells. Extracellular cysteine proteinases from amebic trophozoites are key virulence factors and have a number of important interactions with host defenses, including cleavage of immunoglobulin G (IgG), IgA, and complement components C3 and C5. Amebic lysates have also been shown to activate the precursor to interleukin 1-beta (proIL-1β), mimicking the action of caspase-1. IL-18 is also a central cytokine, which induces gamma interferon (IFN-γ) and activates macrophages, one of the main host defenses against invading trophozoites. Because proIL-18 is also activated by caspase-1, we evaluated whether amebic proteinases had a similar effect. Instead, we found that recombinant proIL-18 was cleaved into smaller fragments by the complex of surface-associated and released amebic proteinases. To evaluate the function of an individual proteinase from the complex pool, we expressed an active surface proteinase, EhCP5, which is functional only in<jats:italic>E. histolytica.</jats:italic>Recombinant EhCP5 expressed in<jats:italic>Pichia pastoris</jats:italic>had kinetic properties similar to those of the native enzyme with respect to substrate specificity and sensitivity to proteinase inhibitors. In contrast to the activation of proIL-1β by amebic lysates, the purified proteinase cleaved proIL-18 and mature IL-18 to biologically inactive fragments. These studies suggest that the acute host response and amebic invasion result from a complex interplay of parasite virulence factors and host defenses.<jats:italic>E. histolytica</jats:italic>may block the host inflammatory response by a novel mechanism, inactivation of IL-18.</jats:p>

収録刊行物

被引用文献 (4)*注記

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ