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

Risultato della ricerca: Other


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 viathe Smad pathway. Increased CCL5 was also observed in bronchi of patientswith 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 collagenproduction in human bronchial epithelial cells (16HBE).Cells were treated with10ng/ml of TGF-β1, 10ng/ml of CCL5 and 10ng/ml of both TGF-β1 and CCL5for 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 significanttime-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 atboth 3h and 24h(p=0.0017 and 0.0433,respectively)and an increase of Smad3mRNA 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 thatTGF-β1 induction of collagen production is mediated mainly by phospho-Smad3. CCL5 inhibits TGF-β1-induced collagen production by modulating Smad activity
Lingua originaleEnglish
Numero di pagine1
Stato di pubblicazionePublished - 2009

Fingerprint Entra nei temi di ricerca di 'CCL5(RANTES) inhibits TGFbeta1 induced collagen production in human bronchial epithelial cells by action of Smad protein'. Insieme formano una fingerprint unica.

Cita questo