RGD Reference Report - Blockade of Th1 chemokine receptors ameliorates pulmonary granulomatosis in mice. - Rat Genome Database

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Blockade of Th1 chemokine receptors ameliorates pulmonary granulomatosis in mice.

Authors: Kishi, J  Nishioka, Y  Kuwahara, T  Kakiuchi, S  Azuma, M  Aono, Y  Makino, H  Kinoshita, K  Kishi, M  Batmunkh, R  Uehara, H  Izumi, K  Sone, S 
Citation: Kishi J, etal., Eur Respir J. 2011 Aug;38(2):415-24. Epub 2011 Jan 27.
RGD ID: 5683877
Pubmed: PMID:21273392   (View Abstract at PubMed)
DOI: DOI:10.1183/09031936.00070610   (Journal Full-text)

Sarcoidosis is a granulomatous disease of unknown aetiology. We identified immunological targets for the treatment of pulmonary granulomatosis using a murine model generated with Propionibacterium acnes. Sensitisation and challenge using heat-killed P. acnes and dendritic cells (DCs) were performed to produce pulmonary granulomatosis in C57BL/6 mice. Immunological analyses using ELISA as well as cDNA microarray analysis were used to search for cytokines or chemokines associated with the formation of granulomas in the lungs. Co-administration of P. acnes and DCs reproducibly induced the formation of pulmonary granulomas, which resembled sarcoid granulomas. The cDNA microarray assay demonstrated that the gene expression of CXCL9 and CXCL10, ligands for CXCR3, and of CCL4, a ligand for CCR5, was strongly upregulated during granulomatosis. ELISA confirmed that levels of CXCL9 and CXCL10 as well as T-helper (Th)1 cytokines and chemokines including tumour necrosis factor-alpha and interferon-gamma were elevated in bronchoalveolar lavage fluid (BALF). The blockade of Th1 chemokine receptors using TAK-779, a dual blocker for CXCR3 and CCR5, led to reduced numbers of CXCR3+CD4+ and CCR5+CD4+ T-cells in BALF. Furthermore, administration of TAK-779 ameliorated the granulomatosis. The targeted inhibition of Th1 chemokines might be useful for inhibiting Th1-biased granulomatous diseases, including sarcoidosis.



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Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
CCL4HumanRespiratory Tract Granuloma  ISORGD:1550761 RGD 
CXCL10HumanRespiratory Tract Granuloma  ISORGD:1550709protein:increased expression:respiratory system fluid/secretionRGD 
CXCL9HumanRespiratory Tract Granuloma  ISORGD:1332044protein:increased expression:respiratory system fluid/secretionRGD 
Ccl4RatRespiratory Tract Granuloma  ISORGD:1550761 RGD 
Ccl4MouseRespiratory Tract Granuloma  IEP  RGD 
Cxcl10RatRespiratory Tract Granuloma  ISORGD:1550709protein:increased expression:respiratory system fluid/secretionRGD 
Cxcl10MouseRespiratory Tract Granuloma  IEP protein:increased expression:respiratory system fluid/secretionRGD 
Cxcl9RatRespiratory Tract Granuloma  ISORGD:1332044protein:increased expression:respiratory system fluid/secretionRGD 
Cxcl9MouseRespiratory Tract Granuloma  IEP protein:increased expression:respiratory system fluid/secretionRGD 
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Genes (Rattus norvegicus)
Ccl4  (C-C motif chemokine ligand 4) Cxcl10  (C-X-C motif chemokine ligand 10) Cxcl9  (C-X-C motif chemokine ligand 9)

Genes (Mus musculus)
Ccl4  (C-C motif chemokine ligand 4) Cxcl10  (C-X-C motif chemokine ligand 10) Cxcl9  (C-X-C motif chemokine ligand 9)

Genes (Homo sapiens)
CCL4  (C-C motif chemokine ligand 4) CXCL10  (C-X-C motif chemokine ligand 10) CXCL9  (C-X-C motif chemokine ligand 9)