Evidence map›Paper›PMID 12595442›Full record

ArticleInfection and immunity2003

A surface amebic cysteine proteinase inactivates interleukin-18.

Xuchu Que, Soo-Hyun Kim, Mohammed Sajid, Lars Eckmann, Charles A Dinarello, James H McKerrow, Sharon L Reed

Open access · greenAbstract read
In one paragraph

Article in Infection and immunity, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.0field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 61 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Cytosolic Recognition of Microbes and Pathogens: Inflammasomes in Action.Microbiology and molecular biology reviews : MMBR · 2018
    Review
  5. Review
  6. Cysteine proteases in protozoan parasites.PLoS neglected tropical diseases · 2018
    Review
  7. Article
  8. Article
  9. Review
  10. Review
  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. How pathogen-derived cysteine proteases modulate host immune responses.Advances in experimental medicine and biology · 2011
    Review
  17. Article
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Xuchu QueDepartment of Pathology, University of California, San Diego, California 92103, USA.
Soo-Hyun Kim
Mohammed Sajid
Lars Eckmann
Charles A Dinarello
James H McKerrow
Sharon L Reed
University of California, San Diego · USUniversity of California, San Francisco · USUniversity of Colorado Health · US

Funding

TL MOLECULES AND GAMMA-DELTA T CELLSP01DK035108 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KAGNOFF, MARTIN FREDERICK · 1986 to 2013
$19.2M
Yeast-based HTS Assay Technologies for ProteasesR01AI015614 · NIAID · UNIVERSITY OF COLORADO DENVER · PI DINARELLO, CHARLES ANTHONY · 1985 to 2025
$8.5M
X-RAY CRYSTALLOGRAPHYP01AI035707 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ROUSH, WILLIAM R · 1995 to 2008
$7.8M
Genetic Manipulation of Entamoeba VirulenceR01AI049531 · NIAID · UNIVERSITY OF CALIFORNIA SAN DIEGO · PI REED, SHARON L · 2001 to 2005
$1.4M
CYSTEINE PROTEINASES AND VIRULENCE OF E. HISTOLYTICAR21AI028035 · NIAID · UNIVERSITY OF CALIFORNIA SAN DIEGO · PI REED, SHARON L · 2000 to 2000
$336k
Pathogenesis of Fever in ManR56AI015614 · NIAID · UNIVERSITY OF COLORADO DENVER · PI DINARELLO, CHARLES ANTHONY · 2016 to 2016
$311k
CYSTEINE PROTEINASES AND VIRULENCE OF E. HISTOLYTICAR01AI028035 · NIAID · UNIVERSITY OF CALIFORNIA SAN DIEGO · PI REED, SHARON L · 1990 to 1998
–
PATHOGENESIS OF FEVER IN HUMANSR37AI015614 · NIAID · UNIVERSITY OF COLORADO DENVER · PI DINARELLO, CHARLES ANTHONY · 1988 to 1998
–
NIAID NIH HHS AI-15614NIAID NIH HHS AI-28035NIAID NIH HHS AI-35707NIAID NIH HHS AI-49531NIAID NIH HHS P01 AI035707NIAID NIH HHS R01 AI015614NIAID NIH HHS R01 AI049531NIAID NIH HHS R56 AI015614NIDDK NIH HHS DK-35108NIDDK NIH HHS P01 DK035108
6 · The paper itself

Abstract

Amebiasis is a major cause of morbidity and mortality worldwide. Invasion by Entamoeba histolytica 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-1beta), mimicking the action of caspase-1. IL-18 is also a central cytokine, which induces gamma interferon (IFN-gamma) 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 E. histolytica. Recombinant EhCP5 expressed in Pichia pastoris 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-1beta 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. E. histolytica may block the host inflammatory response by a novel mechanism, inactivation of IL-18.

Indexed as

Amino Acid SequenceAnimalsCell LineCysteine EndopeptidasesEntamoeba histolyticaHumansHydrogen-Ion ConcentrationInterleukin-12Interleukin-18KineticsMolecular Sequence DataProtozoan ProteinsRabbitsSubstrate SpecificityCysteine EndopeptidasesInterleukin-12Interleukin-18Protozoan Proteins

Identifiers

PMID12595442
PMCPMC148873
OpenAlexW2105569385

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.