Rituximab ameliorates skin fibrosis through regulating myofibroblasts activity and TGF- β1 differentiation in bleomycin-induced experimental scleroderma model


Karatas A., Dik Y., Özgen M., Oz B., Onalan E., Gozel N., ...Daha Fazla

Fresenius Environmental Bulletin, cilt.30, sa.6, ss.5645-5650, 2021 (SCI-Expanded) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 30 Sayı: 6
  • Basım Tarihi: 2021
  • Dergi Adı: Fresenius Environmental Bulletin
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Aerospace Database, Aqualine, Aquatic Science & Fisheries Abstracts (ASFA), CAB Abstracts, Chemical Abstracts Core, Communication Abstracts, Environment Index, Geobase, Greenfile, Metadex, Pollution Abstracts, Veterinary Science Database, Civil Engineering Abstracts
  • Sayfa Sayıları: ss.5645-5650
  • Anahtar Kelimeler: Bleomycin, Rituximab, Scleroderma
  • Ondokuz Mayıs Üniversitesi Adresli: Evet

Özet

Scleroderma (systemic sclerosis) is a chronic inflammatory disease that progresses with vascular damage, immunological abnormalities, and extensive fibrosis. Rituximab, an antibody against the B- lymphocyte-specific CD20 surface marker leads to depletion of B cell counts and functions. This study aims to investigate the protective efficacy of rituximab on skin fibrosis in bleomycin (BLM) -induced experimental scleroderma model. This study included 4 groups of (n=7 for each group) Balb/c mice. Group I mice were treated with subcutaneous 100 μl/day phosphate-buffered saline (PBS); while mice in Groups II, III, and IV were treated with subcutaneous 100 μl/day BLM. Mice in Group III and Group IV were treated, intraperitoneally, with 50 μg and 250 μg rituximab, respectively; on the 1st and 14th days of the experiment. Mice in all groups were sacrificed at the end of the 4-week experimental period and tissue specimens were obtained. Serum levels of transforming growth factor (TGF)-beta;l, dermal thickness, the number of dermal inflammatory cells, and the number of a smooth muscle actin positive cells (α-SMA+) were determined. The administration of BLM increased the inflammatory cell infiltration of the dermis, α-SMA+ cell counts in the dermis, and dermal thickness. However, rituximab treatments decreased inflammatory cell infiltrations, α-SMA+ cell counts and dermal thickness, in the BLM injected mice. Both rituximab doses had similar antifibrotic efficacy. Rituximab prevents the development of fibrosis in a BLM-induced experimental scleroderma model. This result suggests that rituximab may be a effective therapeutic agent in patients with early-stage scleroderma.