Role of transforming growth factor-β1 in down-regulating TNF production by alveolar macrophages during asbestos-induced pulmonary fibrosis
Activation of alveolar macrophages (AM) for tumour necrosis factor production is suppressed initially during the inflammatory response to fibrogenic dusts. We investigated the mechanisms involved in TNF suppression, notably the role of other AM-derived mediators including prostaglandin E2 (PGE2), tr...
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| Format: | Article |
| Language: | English |
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Wiley
1996-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/S0962935196000063 |
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| author | Irma Lemaire Sophie Ouellet |
| author_facet | Irma Lemaire Sophie Ouellet |
| author_sort | Irma Lemaire |
| collection | DOAJ |
| description | Activation of alveolar macrophages (AM) for tumour necrosis factor production is suppressed initially during the inflammatory response to fibrogenic dusts. We investigated the mechanisms involved in TNF suppression, notably the role of other AM-derived mediators including prostaglandin E2 (PGE2), transforming growth factor-β1 (TGF-β1), and interleukin 6 (IL-6). The action of PGE2 and TGF-β1, on AM was different. At physiologically relevant doses (25–300 pg/ml), PGE2 did not cause significant inhibition of Hpopolysaccharide (Lps)-induced TNF release by AM in vitro but stimulated IL-6 (up to six fold), an inhibitor of AM-derived TNT. In contrast, TGF-β1 (0.5–50 ng/ml) inhibited both LPS-induced TNT and IL-6 release by 50% but had no effect on PGE2 production by AM. To determine the respective contribution of these different inhibitors in TNF suppression, AM from rats exposed to fibrogenic asbestos for weeks were treated with neutralizing antibody against TGF-β1 or indomethacin, an inhibitor of PGE2 synthesis. Treatment of rat AM with anti-TGF-β1 but not indomethacin, abrogated the observed TNT suppression. These results suggest that an autocrine, TGF-β1-dependent mechanism is involved in the down-regulation of TNF production by rat AM from animals with lung fibrosis. |
| format | Article |
| id | doaj-art-4577d2cb292644e0bc90b76e2947e2af |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 1996-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-4577d2cb292644e0bc90b76e2947e2af2025-02-03T01:06:59ZengWileyMediators of Inflammation0962-93511466-18611996-01-0151374210.1155/S0962935196000063Role of transforming growth factor-β1 in down-regulating TNF production by alveolar macrophages during asbestos-induced pulmonary fibrosisIrma Lemaire0Sophie Ouellet1Laboratory of Immunopharmacology, Department of Pharmacology, Faculty of Medicine, University of Ottawa, Ottawa K1H 8M5, CanadaLaboratory of Immunopharmacology, Department of Pharmacology, Faculty of Medicine, University of Ottawa, Ottawa K1H 8M5, CanadaActivation of alveolar macrophages (AM) for tumour necrosis factor production is suppressed initially during the inflammatory response to fibrogenic dusts. We investigated the mechanisms involved in TNF suppression, notably the role of other AM-derived mediators including prostaglandin E2 (PGE2), transforming growth factor-β1 (TGF-β1), and interleukin 6 (IL-6). The action of PGE2 and TGF-β1, on AM was different. At physiologically relevant doses (25–300 pg/ml), PGE2 did not cause significant inhibition of Hpopolysaccharide (Lps)-induced TNF release by AM in vitro but stimulated IL-6 (up to six fold), an inhibitor of AM-derived TNT. In contrast, TGF-β1 (0.5–50 ng/ml) inhibited both LPS-induced TNT and IL-6 release by 50% but had no effect on PGE2 production by AM. To determine the respective contribution of these different inhibitors in TNF suppression, AM from rats exposed to fibrogenic asbestos for weeks were treated with neutralizing antibody against TGF-β1 or indomethacin, an inhibitor of PGE2 synthesis. Treatment of rat AM with anti-TGF-β1 but not indomethacin, abrogated the observed TNT suppression. These results suggest that an autocrine, TGF-β1-dependent mechanism is involved in the down-regulation of TNF production by rat AM from animals with lung fibrosis.http://dx.doi.org/10.1155/S0962935196000063 |
| spellingShingle | Irma Lemaire Sophie Ouellet Role of transforming growth factor-β1 in down-regulating TNF production by alveolar macrophages during asbestos-induced pulmonary fibrosis Mediators of Inflammation |
| title | Role of transforming growth factor-β1 in down-regulating TNF production by alveolar macrophages during asbestos-induced pulmonary fibrosis |
| title_full | Role of transforming growth factor-β1 in down-regulating TNF production by alveolar macrophages during asbestos-induced pulmonary fibrosis |
| title_fullStr | Role of transforming growth factor-β1 in down-regulating TNF production by alveolar macrophages during asbestos-induced pulmonary fibrosis |
| title_full_unstemmed | Role of transforming growth factor-β1 in down-regulating TNF production by alveolar macrophages during asbestos-induced pulmonary fibrosis |
| title_short | Role of transforming growth factor-β1 in down-regulating TNF production by alveolar macrophages during asbestos-induced pulmonary fibrosis |
| title_sort | role of transforming growth factor β1 in down regulating tnf production by alveolar macrophages during asbestos induced pulmonary fibrosis |
| url | http://dx.doi.org/10.1155/S0962935196000063 |
| work_keys_str_mv | AT irmalemaire roleoftransforminggrowthfactorb1indownregulatingtnfproductionbyalveolarmacrophagesduringasbestosinducedpulmonaryfibrosis AT sophieouellet roleoftransforminggrowthfactorb1indownregulatingtnfproductionbyalveolarmacrophagesduringasbestosinducedpulmonaryfibrosis |