Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P10145 (
IL-8
)
23,849
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Helicobacter pylori has been widely recognized as an important human pathogen responsible for chronic gastritis, peptic ulcers, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma. Little is known about the natural history of this infection since patients are usually recognized as having the infection only after years or decades of chronic disease. Several animal models of H. pylori infection, including those with different species of rodents, nonhuman primates, and germ-free animals, have been developed. Here we describe a new animal model in which the clinical, pathological, microbiological, and immunological aspects of human acute and chronic infection are mimicked and which allows us to monitor these aspects of infection within the same individuals. Conventional Beagle dogs were infected orally with a mouse-adapted strain of H. pylori and monitored for up to 24 weeks.
Acute infection
caused vomiting and diarrhea. The acute phase was followed by polymorphonuclear cell infiltration,
interleukin 8
induction, mononuclear cell recruitment, and the appearance of a specific antibody response against H. pylori. The chronic phase was characterized by gastritis, epithelial alterations, superficial erosions, and the appearance of the typical macroscopic follicles that in humans are considered possible precursors of MALT lymphoma. In conclusion, infection in this model mimics closely human infection and allows us to study those phases that cannot be studied in humans. This new model can be a unique tool for learning more about the disease and for developing strategies for treatment and prevention.
...
PMID:A conventional beagle dog model for acute and chronic infection with Helicobacter pylori. 1033 28
Respiratory infection by Actinobacillus pleuropneumoniae causes a highly pathogenic necrotizing pleuropneumonia with severe edema, hemorrhage and fever.
Acute infection
is characterized by expression of inflammatory cytokines, including interleukin-1 (IL-1), IL-6 and
IL-8
. To determine if high level production of inflammatory cytokines contributed to disease pathogenesis, we investigated if inhibiting macrophage activation with adenovirus type 5-expressed IL-10 (Ad-5/IL-10) reduced the severity of acute disease. Porcine tracheal epithelial cells infected with Ad-5/IL-10 produced bioactive human IL-10. When pigs were intratracheally infected with A. pleuropneumoniae, pigs pretreated with Ad-5/IL-10 showed a significant reduction in the amount of lung damage when compared to adenovirus type 5-expressing beta-galactosidase (Ad-5/beta-Gal)-treated and untreated pigs. In addition, serum zinc levels were unchanged, the lung weight/body weight ratio (an indicator of vascular leakage) was significantly reduced, and lung pathology scores were reduced. Myeloperoxidase activity in lung lavage fluid samples, an indicator of neutrophil invasion, was decreased to levels similar to that seen in pigs not infected with A. pleuropneumoniae. Reduction in inflammatory cytokine levels in lung lavage fluid samples correlated with the clinical observations in that pigs pretreated with Ad-5/IL-10 showed a corresponding reduction of IL-1 and tumor necrosis factor (TNF) compared with untreated and Ad-5/beta-Gal-treated pigs. IL-6 levels were unaffected by pretreatment with Ad-5/IL-10, consistent with observations that IL-6 was not derived from alveolar macrophages. Since inflammatory cytokines are expressed at high levels in acute bacterial pleuropneumonia, these results indicate that macrophage activation, involving overproduction of IL-1 and TNF, is a prime factor in infection-related cases of massive lung injury.
...
PMID:Interleukin-10 gene therapy-mediated amelioration of bacterial pneumonia. 1089 82
The intestinal protozoan parasite
Entamoeba histolytica
(
Eh
) causes amebiasis associated with severe diarrhea and/or liver abscess.
Eh
pathogenesis is multifactorial requiring both parasite virulent molecules and host-induced innate immune responses.
Eh
-induced host pro-inflammatory responses plays a critical role in disease pathogenesis by causing damage to tissues allowing parasites access to systemic sites.
Eh
cyclooxygenase (
Eh
Cox) derived prostaglandin E
2
stimulates the chemokine
IL-8
from mucosal epithelial cells that recruits neutrophils to the site of infection to exacerbate disease. At present, it is not known how
Eh
Cox is regulated or whether it affects the expression of other proteins in
Eh
. In this study, we found that gene silencing of
Eh
Cox (
EhCoxgs
) markedly increased endogenous cysteine protease (CP) protein expression and virulence without altering CP gene transcripts. Live virulent
Eh
pretreated with arachidonic acid substrate to enhance PGE
2
production or aspirin to inhibit
Eh
Cox enzyme activity or addition of exogenous PGE
2
to
Eh
had no effect on
Eh
CP activity. Increased CP enzyme activity in
EhCoxgs
was stable and significantly enhanced erythrophagocytosis, cytopathic effects on colonic epithelial cells and elicited pro-inflammatory cytokines in mice colonic loops.
Acute infection
with
EhCoxgs
in colonic loops increased inflammation associated with high levels of myeloperoxidase activity. This study has identified
Eh
Cox protein as one of the important endogenous regulators of cysteine protease activity. Alterations of CP activity in response to Cox gene silencing may be a negative feedback mechanism in
Eh
to limit proteolytic activity during colonization that can inadvertently trigger inflammation in the gut.
...
PMID:
Entamoeba histolytica
Cyclooxygenase-Like Protein Regulates Cysteine Protease Expression and Virulence. 3068 44
