RGD Reference Report - Role of proinflammatory cytokines IL-18 and IL-1beta in bleomycin-induced lung injury in humans and mice. - Rat Genome Database

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Role of proinflammatory cytokines IL-18 and IL-1beta in bleomycin-induced lung injury in humans and mice.

Authors: Hoshino, T  Okamoto, M  Sakazaki, Y  Kato, S  Young, HA  Aizawa, H 
Citation: Hoshino T, etal., Am J Respir Cell Mol Biol. 2009 Dec;41(6):661-70. Epub 2009 Mar 5.
RGD ID: 4889574
Pubmed: PMID:19265174   (View Abstract at PubMed)
DOI: DOI:10.1165/rcmb.2008-0182OC   (Journal Full-text)

Administration of several chemotherapeutic drugs, such as bleomycin, busulfan, and gefitinib, often induces lethal lung injury. However, the precise mechanisms responsible for this drug-induced lung injury are still unclear. In the present study, we examined the role of the proinflammatory cytokines IL-18 and IL-1beta in the mechanism of bleomycin-induced lung injury. We performed immunohistochemical analysis of IL-18 and IL-18 receptor (R) alpha chain expression in the lungs of five patients with bleomycin-induced lethal lung injury. Enhanced expression of both IL-18 and IL-18Ralpha was observed in the lungs of all five patients with bleomycin-induced lung injury. To support the data obtained from patient samples, the levels of IL-1beta and IL-18 mRNA and protein, pulmonary inflammation, and lung fibrosis were examined in mouse models of bleomycin-induced lung injury. Intravenous administration of bleomycin induced the expression of IL-1beta and IL-18 in the serum and lungs of wild-type C57BL/6 mice. IL-18-producing F4/80(+) neutrophils, but not CD3(+) T cells, were greatly increased in the lungs of treated mice. Moreover, bleomycin-induced lung injury was significantly attenuated in caspase-1(-/-), IL-18(-/-), and IL-18Ralpha(-/-) mice in comparison with control mice. Thus, our results provide evidence for an important role of IL-1beta and IL-18 in chemotherapy-induced lung injury.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
lung disease  ISOCasp1 (Mus musculus)4889574; 4889574 RGD 
lung disease  IMP 4889574 RGD 
lung disease  ISOIl18 (Mus musculus)4889574; 4889574lung injuryRGD 
lung disease  IEP 4889574lung injury and protein:increased expression:lung RGD 
lung disease  IEP 4889574Lung Injury and protein:increased expression:lung RGD 
lung disease  ISOIL18 (Homo sapiens)4889574; 4889574lung injury and protein:increased expression:lung RGD 
lung disease  IMP 4889574lung injuryRGD 
lung disease  ISOIl18r1 (Mus musculus) and IL18R1 (Homo sapiens)4889574Lung InjuryRGD 
lung disease  IMP 4889574Lung InjuryRGD 

Objects Annotated

Genes (Rattus norvegicus)
Casp1  (caspase 1)
Il18  (interleukin 18)
Il18r1  (interleukin 18 receptor 1)

Genes (Mus musculus)
Casp1  (caspase 1)
Il18  (interleukin 18)
Il18r1  (interleukin 18 receptor 1)

Genes (Homo sapiens)
CASP1  (caspase 1)
IL18  (interleukin 18)
IL18R1  (interleukin 18 receptor 1)


Additional Information