Alveolar epithelial cells in idiopathic pulmonary fibrosis display upregulation of TRAIL, DR4 and DR5 expression with simultaneous preferential over-expression of pro-apoptotic marker p53

作者: Nicola J Lomas , Monica A Spiteri , Nicholas R Forsyth , Khondoker M Akram

DOI:

关键词:

摘要: Idiopathic pulmonary fibrosis (IPF) is a progressive, debilitating, and fatal lung disease of unknown aetiology with no current cure. The pathogenesis IPF remains unclear but repeated alveolar epithelial cell (AEC) injuries subsequent apoptosis are believed to be among the initiating/ongoing triggers. However, precise mechanism apoptotic induction hitherto elusive. In this study, we investigated expression panel pro-apoptotic cycle regulatory proteins in 21 19 control tissue samples. We reveal significant upregulation apoptosis-inducing ligand TRAIL its cognate receptors DR4 DR5 AEC within active lesions lungs. This was accompanied by protein p53 overexpression. contrast, myofibroblasts fibroblastic foci lungs exhibited high TRAIL, negligible expression. Similarly, absent or macrophages lymphocytes. No differences were noted these types between detected marker cellular senescence p21WAF1 upregulated affected Cell Cyclin D1 SOCS3 significantly enhanced remodelled fibrotic areas myofibroblasts. Taken together findings suggest that, IPF, can display markers associated proliferation, senescence, apoptotosis, where could drive response. Clear understanding processes identification therapeutic targets will direct us develop effective therapies for IPF.

参考文章(63)
Henning Walczak, Robert E. Miller, Kiley Ariail, Brian Gliniak, Thomas S. Griffith, Marek Kubin, Wilson Chin, Jon Jones, Anne Woodward, Tiep Le, Craig Smith, Pam Smolak, Raymond G. Goodwin, Charles T. Rauch, JoAnn C.L. Schuh, David H. Lynch, Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo Nature Medicine. ,vol. 5, pp. 157- 163 ,(1999) , 10.1038/5517
Heinz Fehrenbach, Alveolar epithelial type II cell: defender of the alveolus revisited Respiratory Research. ,vol. 2, pp. 33- 46 ,(2001) , 10.1186/RR36
Nicola J Lomas, Monica A Spiteri, Nicholas R Forsyth, Khondoker M Akram, Keira L Watts, Idiopathic pulmonary fibrosis: immunohistochemical analysis provides fresh insights into lung tissue remodelling with implications for novel prognostic markers International Journal of Clinical and Experimental Pathology. ,vol. 5, pp. 58- 71 ,(2012)
Moisés Selman, Annie Pardo, None, Idiopathic pulmonary fibrosis: an epithelial/fibroblastic cross-talk disorder Respiratory Research. ,vol. 3, pp. 3- 3 ,(2001) , 10.1186/RR175
Minji Jo, Tae-Hyoung Kim, Dai-Wu Seol, James E. Esplen, Kenneth Dorko, Timothy R. Billiar, Stephen C. Strom, Apoptosis induced in normal human hepatocytes by tumor necrosis factor-related apoptosis-inducing ligand Nature Medicine. ,vol. 6, pp. 564- 567 ,(2000) , 10.1038/75045
Bert Vogelstein, David Sidransky, Ruth W. Craig, Michael B. Kastan, Onyinye Onyekwere, Participation of p53 Protein in the Cellular Response to DNA Damage Cancer Research. ,vol. 51, pp. 6304- 6311 ,(1991)
Jennet M. Harvey, Gary M. Clark, C. Kent Osborne, D. Craig Allred, Estrogen Receptor Status by Immunohistochemistry Is Superior to the Ligand-Binding Assay for Predicting Response to Adjuvant Endocrine Therapy in Breast Cancer Journal of Clinical Oncology. ,vol. 17, pp. 1474- 1474 ,(1999) , 10.1200/JCO.1999.17.5.1474
J. R. G. NASH, P. J. MCLAUGHLIN, D. BUTCHER, B. CORRIN, Expression of tumour necrosis factor-α in cryptogenic fibrosing alveolitis Histopathology. ,vol. 22, pp. 343- 347 ,(1993) , 10.1111/J.1365-2559.1993.TB00133.X
Michael A. O'Reilly, Rhonda J. Staversky, Richard H. Watkins, Christina K. Reed, Karen L. de Mesy Jensen, Jacob N. Finkelstein, Peter C. Keng, The cyclin-dependent kinase inhibitor p21 protects the lung from oxidative stress. American Journal of Respiratory Cell and Molecular Biology. ,vol. 24, pp. 703- 710 ,(2001) , 10.1165/AJRCMB.24.6.4355
Neil A. Fanger, Charles R. Maliszewski, Ken Schooley, Thomas S. Griffith, HUMAN DENDRITIC CELLS MEDIATE CELLULAR APOPTOSIS VIA TUMOR NECROSIS FACTOR-RELATED APOPTOSIS-INDUCING LIGAND (TRAIL) Journal of Experimental Medicine. ,vol. 190, pp. 1155- 1164 ,(1999) , 10.1084/JEM.190.8.1155