RGD Reference Report - Allergen challenge induces Ifng dependent GTPases in the lungs as part of a Th1 transcriptome response in a murine model of allergic asthma. - Rat Genome Database

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Allergen challenge induces Ifng dependent GTPases in the lungs as part of a Th1 transcriptome response in a murine model of allergic asthma.

Authors: Dharajiya, N  Vaidya, S  Sinha, M  Luxon, B  Boldogh, I  Sur, S 
Citation: Dharajiya N, etal., PLoS One. 2009 Dec 21;4(12):e8172.
RGD ID: 5130978
Pubmed: PMID:20027288   (View Abstract at PubMed)
PMCID: PMC2791840   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0008172   (Journal Full-text)

According to the current paradigm, allergic airway inflammation is mediated by Th2 cytokines and pro-inflammatory chemokines. Since allergic inflammation is self-limited, we hypothesized that allergen challenge simultaneously induces anti-inflammatory genes to counter-balance the effects of Th2 cytokines and chemokines. To identify these putative anti-inflammatory genes, we compared the gene expression profile in the lungs of ragweed-sensitized mice four hours after challenge with either PBS or ragweed extract (RWE) using a micro-array platform. Consistent with our hypothesis, RWE challenge concurrently upregulated Th1-associated early target genes of the Il12/Stat4 pathway, such as p47 and p65 GTPases (Iigp, Tgtp and Gbp1), Socs1, Cxcl9, Cxcl10 and Gadd45g with the Th2 genes Il4, Il5, Ccl2 and Ccl7. These Th1-associated genes remain upregulated longer than the Th2 genes. Augmentation of the local Th1 milieu by administration of Il12 or CpG prior to RWE challenge further upregulated these Th1 genes. Abolition of the Th1 response by disrupting the Ifng gene increased allergic airway inflammation and abrogated RWE challenge-induced upregulation of GTPases, Cxcl9, Cxcl10 and Socs1, but not Gadd45g. Our data demonstrate that allergen challenge induces two sets of Th1-associated genes in the lungs: 1) Ifng-dependent genes such as p47 and p65 GTPases, Socs1, Cxcl9 and Cxcl10 and 2) Ifng-independent Th1-inducing genes like Gadd45g. We propose that allergen-induced airway inflammation is regulated by simultaneous upregulation of Th1 and Th2 genes, and that persistent unopposed upregulation of Th1 genes resolves allergic inflammation.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
extrinsic allergic alveolitis  ISOCcl7 (Mus musculus)5130978; 5130978 RGD 
extrinsic allergic alveolitis  IEP 5130978 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccl7  (C-C motif chemokine ligand 7)

Genes (Mus musculus)
Ccl7  (C-C motif chemokine ligand 7)

Genes (Homo sapiens)
CCL7  (C-C motif chemokine ligand 7)


Additional Information