Antifibrogenic effects of C‐C chemokine receptor type 2 antagonist in a bleomycin‐induced scleroderma model
Masato Ishikawa, Toshiyuki Yamamoto
Abstract
There have been several studies on the role of the monocyte chemotactic protein-1/C-C chemokine receptor type 2 (CCR2) signalling pathway in fibrotic diseases, which identified the blockade of this pathway as a potential therapeutic target for treating fibrosis. We examined the efficacy of CCR2 antagonist (RS-504393) in a mouse model of scleroderma induced by bleomycin. RS-504393 was administered via intradermal injection 6 hours prior to bleomycin injection, in the same sites. Histopathological examination showed that RS-504393 treatment suppressed dermal fibrosis and decreased dermal thickness. The numbers of mast cells and myofibroblasts in the skin of RS-504393-treated mice were significantly lower compared with those in PBS-treated mice. Moreover, the amount of collagen in the skin of RS-504393-treated mice was significantly lower compared with that in the PBS-treated mice. Additionally, mRNA levels of TGF-β1 and collagen I alpha 1 in sclerotic skin were significantly decreased by RS-504393, and semiquantitative histopathological scoring of the lungs showed inhibition of fibrosis in RS-504393-treated mice. The amount of collagen in the lung of the RS-504393-treated mice was lower compared with that in the PBS-treated mice. These data suggest that CCR2 antagonist RS-504393 may be a therapeutic agent for human scleroderma.