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FRANCESCO CAPPELLO

CCL5(RANTES) inhibits TGFbeta1 induced collagen production in human bronchial epithelial cells by action of Smad protein

  • Autori: Magno, F; La Rocca, G; Anzalone, R; Cappello, F; Zummo, G; Balbi, B; Di Stefano, A; Adcock, I
  • Anno di pubblicazione: 2009
  • Tipologia: Proceedings
  • Parole Chiave: TGF-beta1; smads; COPD; collagen TYPE I

Abstract

Airway epithelial cells modulate bronchial remodelling in COPD and asthma. TGF-β1 up-regulation was observed in the bronchial epithelial cells of asthmatics and COPD patients. TGF-β is involved in airways remodelling mainly acting via the Smad pathway. Increased CCL5 was also observed in bronchi of patients with severe COPD. We investigated the effects of TGF-β1 on collagen type I, Smad 3-4 and 7 expression and the effects of CCL5 on TGF-β1-induced collagen production in human bronchial epithelial cells (16HBE).Cells were treated with 10ng/ml of TGF-β1, 10ng/ml of CCL5 and 10ng/ml of both TGF-β1 and CCL5 for 0,3 and 24 hours.TGF-b1 increased Smad3,Smad4 and collagen type I(p=0.0472, p=0.0433 and p<0.0001,respectively)mRNA at 24h. An increase of Smad7 mRNA was observed at 24h(p=0.0422).We observed a significant time-dependent increase in nuclear phospho-Smad3 at 3h(p=0.0079)and 24h (p=0.0079).Exposure to CCL5 showed an increase of collagen type I mRNA at both 3h and 24h(p=0.0017 and 0.0433,respectively)and an increase of Smad3 mRNA at 3h(p=0.0021. A decrease for Smad7 at both 3h and 24h(p=0.0111 and p=0.0009)was also observed. No changes were observed in nuclear p-Smad3 compared with controls.Combined treatments with CCL5 and TGF-β1 repressed TGF-β1-induced collagen type I,Smad3 and Smad4 mRNA transcription at 24h(p=0.0015, p=0.0367, p=0.0052, respectively, as well as TGF-β1-induced nuclear p-Smad3 protein levels both at 3h and 24h(p=0.0381).Our results indicate that TGF-β1 induction of collagen production is mediated mainly by phospho-Smad3. CCL5 inhibits TGF-β1-induced collagen production by modulating Smad activity

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