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Intensive Care Medicine

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01-01-2005 | Experimental

Active transforming growth factor-β1 activates the procollagen I promoter in patients with acute lung injury

Authors: G. R. Scott Budinger, Navdeep S. Chandel, Helen K. Donnelly, James Eisenbart, Monica Oberoi, Manu Jain

Published in: Intensive Care Medicine | Issue 1/2005

Abstract

Objective

Fibroproliferation markers like procollagen I predict mortality in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). We sought to determine whether bronchoalveolar lavage fluid (BALF) from patients with lung injury contained mediators that would activate procollagen I promoter and if this activation predicted important clinical outcomes.

Design

Prospective controlled study of ALI/ARDS.

Setting

Intensive care units and laboratory of a university hospital.

Patients and participants

Acute lung injury/ARDS, cardiogenic edema (negative controls) and pulmonary fibrosis (positive controls) patients.

Interventions

Bronchoalveolar lavage fluid was collected within 48 h of intubation from ALI/ARDS patients. BALF was also collected from patients with pulmonary fibrosis and cardiogenic pulmonary edema. Human lung fibroblasts were transfected with a procollagen I promoter-luciferase construct and incubated with BALF; procollagen I promoter activity was then measured. BALF active TGF-β1 levels were measured by ELISA.

Results

Twenty-nine ARDS patients, nine negative and six positive controls were enrolled. BALF from ARDS patients induced 41% greater procollagen I promoter activation than that from negative controls (p<0.05) and a TGF-β1 blocking antibody significantly reduced this activation in ARDS patients. There was a trend toward higher TGF-β1 levels in the ARDS group compared to negative controls (−1.056 log₁₀±0.1415 vs −1.505 log₁₀±0.1425) (p<0.09). Procollagen I promoter activation was not associated with mortality; however, lower TGF-β1 levels were associated with more ventilator-free and ICU-free days.

Conclusions

Bronchoalveolar lavage fluid from ALI/ARDS patients activates procollagen I promoter, which is due partly to TGF-β1. Activated TGF-β1 may impact ARDS outcome independent of its effect on procollagen I activation.

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Ware L, Matthay M (2000) The acute respiratory distress syndrome. N Engl J Med 342:1334–1349CrossRefPubMed

The ARDS Network (2000) Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. [see comments]. N Eng J Med 342:1301–1308CrossRef

Davidson TA, Caldwell ES, Curtis JR, Hudson LD, Steinberg KP (1999) Reduced quality of life in survivors of acute respiratory distress syndrome compared with critically ill control patients. JAMA 281:354–360CrossRefPubMed

Herridge MS, Cheung AM, Tansey CM, Matte-Martyn A, Diaz-Granados N, Al-Saidi F, Cooper AB, Guest CB, Mazer CD, Mehta S, Stewart TE, Barr A, Cook D, Slutsky AS (2003) One-year outcomes in survivors of the acute respiratory distress syndrome. N Engl J Med 348:683–693CrossRefPubMed

Slutsky AS, Tremblay LN (1998) Multiple system organ failure. Is mechanical ventilation a contributing factor? Am J Respir Crit Care Med 157:1721–1725PubMed

Montgomery AB, Stager MA, Carrico CJ, Hudson LD (1985) Causes of mortality in patients with the adult respiratory distress syndrome. Am Rev Respir Dis 132:485–489PubMed

Pittet JF, Mackersie RC, Martin TR, Matthay MA (1997) Biological markers of acute lung injury: prognostic and pathogenetic significance. Am J Respir Crit Care Med 155:1187–1205PubMed

Luhr OR, Antonsen K, Karlsson M, Aardal S, Thorsteinsson A, Frostell CG, Bonde J (1999) Incidence and mortality after acute respiratory failure and acute respiratory distress syndrome in Sweden, Denmark and Iceland. The ARF Study Group. Am J Respir Crit Care Med 159:1849–1861PubMed

Doyle RL, Szaflarski N, Modin GW, Wiener-Kronish JP, Matthay MA (1995) Identification of patients with acute lung injury. Predictors of mortality. Am J Respir Crit Care Med 152:1818–1824PubMed

10.

Clark JG, Milberg JA, Steinberg KP, Hudson LD (1995) Type III procollagen peptide in the adult respiratory distress syndrome. Association of increased peptide levels in bronchoalveolar lavage fluid with increased risk for death. Ann Intern Med 122:17–23PubMed

11.

Chesnutt AN, Matthay MA, Tibayan FA, Clark JG (1997) Early detection of type III procollagen peptide in acute lung injury. Pathogenetic and prognostic significance. Am J Respir Crit Care Med 156:840–845PubMed

12.

Meduri GU, Tolley EA, Chinn A, Stentz F, Postlethwaite A (1998) Procollagen types I and III aminoterminal propeptide levels during acute respiratory distress syndrome and in response to methylprednisolone treatment. Am J Respir Crit Care Med 158:1432–1441PubMed

13.

Marshall RP, Bellingan G, Webb S, Puddicombe A, Goldsack N, McAnulty RJ, Laurent GJ (2000) Fibroproliferation occurs early in the acute respiratory distress syndrome and impacts on outcome. Am J Respir Crit Care Med 162:1783–1788PubMed

14.

Hill JD, Ratliff JL, Parrott JC, Lamy M, Fallat RJ, Koeniger E, Yaeger EM, Whitmer G (1976) Pulmonary pathology in acute respiratory insufficiency: lung biopsy as a diagnostic tool. J Thorac Cardiovasc Surg 71:64–71PubMed

15.

Martin C, Papazian L, Payan MJ, Saux P, Gouin F (1995) Pulmonary fibrosis correlates with outcome in adult respiratory distress syndrome. A study in mechanically ventilated patients. [see comments]. Chest 107:196–200PubMed

16.

Nuckton TJ, Alonso JA, Kallet RH, Daniel BM, Pittet J-F, Eisner MD, Matthay MA (2002) Pulmonary dead-space fraction as a risk factor for death in the acute respiratory distress syndrome. New Engl J Med 346:1281–1286CrossRefPubMed

17.

Raghu G, Masta S, Meyers D, Narayanan AS (1989) Collagen synthesis by normal and fibrotic human lung fibroblasts and the effect of transforming growth factor-beta. Am Rev Respir Dis 140:95–100PubMed

18.

Budinger G, Chandel N, Donnelley H, Eisenbart J, Oberoi M, Jain M (2004) Active transforming growth factor-ß1 contributes to procollagen I promoter activation in early lung injury. Am J Respir Crit Care Med 169:A350

19.

Hayashida T, Poncelet AC, Hubchak SC, Schnaper HW (1999) TGF-beta1 activates MAP kinase in human mesangial cells: a possible role in collagen expression. Kidney Int 56:1710–1720CrossRefPubMed

20.

Farjanel J, Hartmann DJ, Guidet B, Luquel L, Offenstadt G (1993) Four markers of collagen metabolism as possible indicators of disease in the adult respiratory distress syndrome. Am Rev Respir Dis 147:1091–1099PubMed

21.

Armstrong L, Thickett DR, Mansell JP, Ionescu M, Hoyle E, Billinghurst RC, Poole AR, Millar AB (1999) Changes in collagen turnover in early acute respiratory distress syndrome. Am J Respir Crit Care Med 160:1910–1915PubMed

22.

Pugin J, Verghese G, Widmer MC, Matthay MA (1999) The alveolar space is the site of intense inflammatory and profibrotic reactions in the early phase of acute respiratory distress syndrome. [see comments]. Crit Care Med 27:304–312

23.

Madtes DK, Rubenfeld G, Klima LD, Milberg JA, Steinberg KP, Martin TR, Raghu G, Hudson LD, Clark JG (1998) Elevated transforming growth factor-alpha levels in bronchoalveolar lavage fluid of patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 158:424–430PubMed

24.

Fahy RJ, Lichtenberger F, McKeegan CB, Nuovo GJ, Marsh CB, Wewers MD (2003) The acute respiratory distress syndrome: a role for transforming growth factor-beta 1. Am J Respir Cell Mol Biol 28:499–503CrossRefPubMed

25.

Nerlich AG, Nerlich ML, Muller PK (1987) Pattern of collagen types and molecular structure of collagen in acute post-traumatic pulmonary fibrosis. Thorax 42:863–869PubMed

26.

Zhao Y, Young SL, McIntosh JC, Steele MP, Silbajoris R (2000) Ontogeny and localization of TGF-beta type I receptor expression during lung development. Am J Physiol Lung Cell Mol Physiol 278:L1231–1239PubMed

27.

Broekelmann TJ, Limper AH, Colby TV, McDonald JA (1991) Transforming growth factor beta 1 is present at sites of extracellular matrix gene expression in human pulmonary fibrosis. Proc Natl Acad Sci U S A 88:6642–6646PubMed

28.

Khalil N, O’Connor RN, Unruh HW, Warren PW, Flanders KC, Kemp A, Bereznay OH, Greenberg AH (1991) Increased production and immunohistochemical localization of transforming growth factor-beta in idiopathic pulmonary fibrosis. Am J Respir Cell Mol Biol 5:155–162PubMed

29.

Hiwatari N, Shimura S, Yamauchi K, Nara M, Hida W, Shirato K (1997) Significance of elevated procollagen-III-peptide and transforming growth factor-beta levels of bronchoalveolar lavage fluids from idiopathic pulmonary fibrosis patients. Tohoku J Exp Med 181:285–295PubMed

30.

Salez F, Gosset P, Copin MC, Lamblin Degros C, Tonnel AB, Wallaert B (1998) Transforming growth factor-beta1 in sarcoidosis. Eur Respir J 12:913–919CrossRefPubMed

31.

Kotecha S, Wangoo A, Silverman M, Shaw RJ (1996) Increase in the concentration of transforming growth factor beta-1 in bronchoalveolar lavage fluid before development of chronic lung disease of prematurity. J Pedriatr 128:464–469

32.

Chambers RC, Dabbagh K, McAnulty RJ, Gray AJ, Blanc-Brude OP, Laurent GJ (1998) Thrombin stimulates fibroblast procollagen production via proteolytic activation of protease-activated receptor 1. Biochem J 333 (Pt 1):121–127PubMed

33.

Pardes JB, Takagi H, Martin TA, Ochoa MS, Falanga V (1995) Decreased levels of alpha 1(I) procollagen mRNA in dermal fibroblasts grown on fibrin gels and in response to fibrinopeptide B. J Cell Physiol 162:9–14PubMed

34.

Krupsky M, Fine A, Kuang PP, Berk JL, Goldstein RH (1996) Regulation of type I collagen production by insulin and transforming growth factor-beta in human lung fibroblasts. Connect Tissue Res 34:53–62PubMed

35.

Telasky C, Tredget EE, Shen Q, Khorramizadeh MR, Iwashina T, Scott PG, Ghahary A (1998) IFN-alpha2b suppresses the fibrogenic effects of insulin-like growth factor-1 in dermal fibroblasts. J Interferon Cytokine Res 18:571–577PubMed

36.

Oriente A, Fedarko NS, Pacocha SE, Huang SK, Lichtenstein LM, Essayan DM (2000) Interleukin-13 modulates collagen homeostasis in human skin and keloid fibroblasts. J Pharmacol Exp Ther 292:988–994PubMed

37.

Doucet C, Brouty-Boye D, Pottin-Clemenceau C, Jasmin C, Canonica GW, Azzarone B (1998) IL-4 and IL-13 specifically increase adhesion molecule and inflammatory cytokine expression in human lung fibroblasts. Int Immunol 10:1421–1433CrossRefPubMed

38.

Last JA, Siefkin AD, Reiser KM (1983) Type I collagen content is increased in lungs of patients with adult respiratory distress syndrome. Thorax 38:364–368PubMed

39.

Greene KE, Wright JR, Steinberg KP, Ruzinski JT, Caldwell E, Wong WB, Hull W, Whitsett JA, Akino T, Kuroki Y, Nagae H, Hudson LD, Martin TR (1999) Serial changes in surfactant-associated proteins in lung and serum before and after onset of ARDS. Am J Respir Crit Care Med 160:1843–1850PubMed

40.

Matute-Bello G, Liles WC, Steinberg KP, Kiener PA, Mongovin S, Chi EY, Jonas M, Martin TR (1999) Soluble Fas ligand induces epithelial cell apoptosis in humans with acute lung injury (ARDS). J Immunol 163:2217–2225PubMed

41.

Ware LB, Matthay MA (2001) Alveolar fluid clearance is impaired in the majority of patients with acute lung injury and the acute respiratory distress syndrome. Am J Respir Crit Care Med 163:1376–1383PubMed

42.

Willis BC, Kim KJ, Li X, Liebler J, Crandall ED, Borok Z (2003) Modulation of ion conductance and active transport by TGF-{beta}1 in alveolar epithelial cell monolayers. Am J Physiol Lung Cell Mol Physiol 285:L1192–L1200PubMed

43.

Pittet JF, Griffiths MJ, Geiser T, Kaminski N, Dalton SL, Huang X, Brown LA, Gotwals PJ, Koteliansky VE, Matthay MA, Sheppard D (2001) TGF-beta is a critical mediator of acute lung injury. J Clin Invest 107:1537–1544PubMed

44.

Fraslon C, Lacaze-Masmonteil T, Zupan V, Chailley-Heu B, Bourbon JR (1993) Fetal rat lung type II cell differentiation in serum-free isolated cell culture: modulation and inhibition. Am J Physiol 264:L504–516PubMed

45.

Hurst VI, Goldberg PL, Minnear FL, Heimark RL, Vincent PA (1999) Rearrangement of adherens junctions by transforming growth factor-beta1: role of contraction. Am J Physiol 276:L582–595PubMed

46.

Das SK, White AC, Fanburg BL (1992) Modulation of transforming growth factor-beta 1 antiproliferative effects on endothelial cells by cysteine, cystine and N-acetylcysteine. J Clin Invest 90:1649–1656PubMed

Title: Active transforming growth factor-β1 activates the procollagen I promoter in patients with acute lung injury
Authors: G. R. Scott Budinger
Navdeep S. Chandel
Helen K. Donnelly
James Eisenbart
Monica Oberoi
Manu Jain
Publication date: 01-01-2005
Publisher: Springer-Verlag
Published in: Intensive Care Medicine / Issue 1/2005
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-004-2503-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Active transforming growth factor-β1 activates the procollagen I promoter in patients with acute lung injury

Abstract

Objective

Design

Setting

Patients and participants

Interventions

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objective

Design

Setting

Patients and participants

Interventions

Results

Conclusions

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