In vitro pharmacoregulation of CC chemokine ligand 5 and its receptor CCR5 in diffuse lung diseases.
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.


CONCLUSIONS
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.
D000328:Adult; D000368:Aged; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002478:Cells, Cultured; D018946:Chemokine CCL5; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism*; D016572:Cyclosporine / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008171:Lung Diseases / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010431:Pentoxifylline / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
C483024:CCL5 protein, human; D018946:Chemokine CCL5; D019742:Chemokines, CC; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D019713:Receptors, CCR5; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D016572:Cyclosporine; D010431:Pentoxifylline