RGD Reference Report - Role of monocyte chemoattractant protein-1 and its receptor,CCR-2, in the pathogenesis of bleomycin-induced scleroderma. - Rat Genome Database

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Role of monocyte chemoattractant protein-1 and its receptor,CCR-2, in the pathogenesis of bleomycin-induced scleroderma.

Authors: Yamamoto, T  Nishioka, K 
Citation: Yamamoto T and Nishioka K, J Invest Dermatol. 2003 Sep;121(3):510-6.
RGD ID: 8661733
Pubmed: PMID:12925209   (View Abstract at PubMed)
DOI: DOI:10.1046/j.1523-1747.2003.12408.x   (Journal Full-text)

Systemic sclerosis is a connective tissue disease characterized by excessive deposition of extracellular matrix in the skin as well as various internal organs. Cellular infiltrates are found in the dermis in early systemic sclerosis, which are suggested to play an important part. Recent studies suggest the involvement of monocyte chemoattractant protein-1, a C-C chemokine, in the fibrotic process. This study examines the role of monocyte chemoattractant protein-1 in the induction of dermal sclerosis in a murine model of bleomycin-induced scleroderma. Immunohistochemical analysis showed that expression of monocyte chemoattractant protein-1 in the infiltrating mononuclear cells was enhanced at 2 to 3 wk following bleomycin treatment, whereas expression of monocyte chemoattractant protein-1 in fibroblasts was detected at later stages in the sclerotic skin. Reverse transcriptase-polymerase chain reaction analysis showed that monocyte chemoattractant protein-1 mRNA expression in the lesional skin peaked at 2 to 3 wk following bleomycin treatment. Expression of CCR-2, a major receptor for monocyte chemo-attractant protein-1, was also upregulated in the lesional skin at both protein and mRNA levels following bleomycin treatment. Administration of anti-monocyte chemoattractant protein-1 neutralizing antibody together with local bleomycin treatment reduced dermal sclerosis, along with a decrease of collagen content in the skin as well as mRNA expression of type I collagen. In vitro analysis showed that stimulation with monocyte chemoattractant protein-1 (10 ng per mL) upregulated alpha1(I) collagen and decorin mRNA expression in normal dermal fibroblasts, whereas mRNA levels of fibronectin and biglycan were not altered. These data suggest that monocyte chemoattractant protein-1 and CCR-2 signaling plays an important part in the pathogenesis of bleomycin-induced scleroderma. Monocyte chemoattractant protein-1 may contribute to the induction of dermal sclerosis via its direct effect of upregulation of mRNA expression of extracellular matrix on fibroblasts, as well as indirect effect mediated by a number of cytokines released from immunocytes recruited into the lesional skin.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CCL2Humanlimited scleroderma  ISOCcl2 (Mus musculus)mRNA and protein:increased expression:skinRGD 
CCR2Humanlimited scleroderma  ISOCcr2 (Mus musculus)mRNA and protein:increased expression:skin:RGD 
Ccl2Ratlimited scleroderma  ISOCcl2 (Mus musculus)mRNA and protein:increased expression:skin:RGD 
Ccl2Mouselimited scleroderma  IEP mRNA and protein:increased expression:skin:RGD 
Ccl2Mouselimited scleroderma  IMP  RGD 
Ccr2Ratlimited scleroderma  ISOCcr2 (Mus musculus)mRNA and protein:increased expression:skin:RGD 
Ccr2Mouselimited scleroderma  IEP mRNA and protein:increased expression:skin:RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccl2  (C-C motif chemokine ligand 2)
Ccr2  (C-C motif chemokine receptor 2)

Genes (Mus musculus)
Ccl2  (C-C motif chemokine ligand 2)
Ccr2  (C-C motif chemokine receptor 2)

Genes (Homo sapiens)
CCL2  (C-C motif chemokine ligand 2)
CCR2  (C-C motif chemokine receptor 2)

Objects referenced in this article
Gene CCL13 C-C motif chemokine ligand 13 Homo sapiens

Additional Information