BACKGROUND: CC chemokine ligand (CCL)5 and its receptor CCR5 contribute to leukocyte migration into lungs of patients with diffuse lung diseases (DLD). Pharmacological regulation of CCL5 and CCR5 expression was therefore explored in bronchoalveolar cells obtained from patients with DLD. METHODS: Cells from 21 patients were co-cultivated in vitro with tumour necrosis factor-alpha and dexamethasone, cyclosporin A (CyA) or pentoxifylline. Chemokine mRNA expression and protein production was assessed by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. RESULTS: Dexamethasone altered CCL5 mRNA expression and suppressed its protein levels. CyA inhibited chemokine mRNA expression but not protein production. Pentoxifylline did not affected chemokine expression. Both dexamethasone and CyA suppressed CCR5 mRNA transcripts. CONCLUSION: In conclusion, while dexamethasone downregulates the CCL5 functional form, CyA and pentoxifylline have no effects on CCL5 protein. These data provide in vitro correlation for clinical applications of immunomodulators in therapy of DLD.
BACKGROUND:CC chemokine ligand (CCL)5 and its receptor CCR5 contribute to leukocyte migration into lungs of patients with diffuse lung diseases (DLD). Pharmacological regulation of CCL5 and CCR5 expression was therefore explored in bronchoalveolar cells obtained from patients with DLD. METHODS: Cells from 21 patients were co-cultivated in vitro with tumour necrosis factor-alpha and dexamethasone, cyclosporin A (CyA) or pentoxifylline. Chemokine mRNA expression and protein production was assessed by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. RESULTS:Dexamethasone altered CCL5 mRNA expression and suppressed its protein levels. CyA inhibited chemokine mRNA expression but not protein production. Pentoxifylline did not affected chemokine expression. Both dexamethasone and CyA suppressed CCR5 mRNA transcripts. CONCLUSION: In conclusion, while dexamethasone downregulates the CCL5 functional form, CyA and pentoxifylline have no effects on CCL5 protein. These data provide in vitro correlation for clinical applications of immunomodulators in therapy of DLD.
Authors: Martin Petrek; Agata Gibejova; Jiri Drabek; Frantisek Mrazek; Vitezslav Kolek; Evzen Weigl; Roland M du Bois Journal: Immunol Lett Date: 2002-03-01 Impact factor: 3.685
Authors: Agata Gibejova; Frantisek Mrazek; Daniela Subrtova; Veronika Sekerova; Jaroslava Szotkowska; Vitezslav Kolek; Roland M du Bois; Martin Petrek Journal: Am J Respir Crit Care Med Date: 2003-03-05 Impact factor: 21.405
Authors: N Poulakis; G Androutsos; D Kazi; A Bastas; A Provata; C Bitsakou; T Kontozoglou; C Polyzogopoulou; A Tassiopoulou Journal: Respir Med Date: 1999-01 Impact factor: 3.415