help button home button Am J Pathol Epitomics, Inc.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Material
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Saika, S.
Right arrow Articles by Kao, W. W.-Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Saika, S.
Right arrow Articles by Kao, W. W.-Y.
(American Journal of Pathology. 2006;168:1848-1860.)
© 2006 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2006.050980

Loss of Tumor Necrosis Factor {alpha} Potentiates Transforming Growth Factor ß-mediated Pathogenic Tissue Response during Wound Healing

Shizuya Saika*, Kazuo Ikeda{dagger}, Osamu Yamanaka*, Kathleen C. Flanders{ddagger}, Yuka Okada*, Takeshi Miyamoto*, Ai Kitano*, Akira Ooshima§, Yuji Nakajima{dagger}, Yoshitaka Ohnishi* and Winston W.-Y. Kao

From the Departments of Ophthalmology* and Pathology,§ Wakayama Medical University, Wakayama, Japan; the Department of Anatomy,{dagger} Graduate School of Medicine, Osaka City University, Osaka, Japan; the Laboratory of Cell Regulation and Carcinogenesis,{ddagger} National Cancer Institute, National Institutes of Health, Bethesda, Maryland; and the Department of Ophthalmology, University of Cincinnati Medical Center, Cincinnati, Ohio

Animal cornea is an avascular transparent tissue that is suitable for research on wound healing-related scarring and neovascularization. Here we show that loss of tumor necrosis factor {alpha} (TNF{alpha}) potentiates the undesirable, pathogenic response of wound healing in an alkali-burned cornea in mice. Excessive invasion of macrophages and subsequent formation of a vascularized scar tissue were much more marked in TNF{alpha}-null knockout (KO) mice than in wild-type mice. Such an unfavorable outcome in KO mice was abolished by Smad7 gene introduction, indicating the involvement of transforming growth factor ß or activin/Smad signaling. Bone marrow transplantation from wild-type mice normalized healing of the KO mice, suggesting the involvement of bone marrow-derived inflammatory cells in this phenomenon. Co-culture experiments showed that loss of TNF{alpha} in macrophages, but not in fibroblasts, augmented the fibroblast activation as determined by detection of {alpha}-smooth muscle actin, the hallmark of myofibroblast generation, mRNA expression of collagen I{alpha}2 and connective tissue growth factor, and detection of collagen protein. TNF{alpha} in macrophages may be required to suppress undesirable excessive inflammation and scarring, both of which are promoted by transforming growth factor ß, and for restoration of tissue architecture in a healing alkali-burned cornea in mice.




This article has been cited by other articles:


Home page
 IOVSHome page
N. Fujita, S. Fujita, Y. Okada, K. Fujita, A. Kitano, O. Yamanaka, T. Miyamoto, S. Kon, T. Uede, S. R. Rittling, et al.
Impaired Angiogenic Response in the Corneas of Mice Lacking Osteopontin
Invest. Ophthalmol. Vis. Sci., February 1, 2010; 51(2): 790 - 794.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
V. P. J. Saw, R. J. C. Dart, G. Galatowicz, J. T. Daniels, J. K. G. Dart, and V. L. Calder
Tumor Necrosis Factor-{alpha} in Ocular Mucous Membrane Pemphigoid and Its Effect on Conjunctival Fibroblasts
Invest. Ophthalmol. Vis. Sci., November 1, 2009; 50(11): 5310 - 5317.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
X. Liu, R. J. Kelm Jr., and A. R. Strauch
Transforming Growth Factor {beta}1-mediated Activation of the Smooth Muscle {alpha}-Actin Gene in Human Pulmonary Myofibroblasts Is Inhibited by Tumor Necrosis Factor-{alpha} via Mitogen-activated Protein Kinase Kinase 1-dependent Induction of the Egr-1 Transcriptional Repressor
Mol. Biol. Cell, April 15, 2009; 20(8): 2174 - 2185.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
U. Pattamatta, M. Willcox, F. Stapleton, N. Cole, and Q. Garrett
Bovine Lactoferrin Stimulates Human Corneal Epithelial Alkali Wound Healing In Vitro
Invest. Ophthalmol. Vis. Sci., April 1, 2009; 50(4): 1636 - 1643.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
K.-i. Miyazaki, Y. Okada, O. Yamanaka, A. Kitano, K. Ikeda, S. Kon, T. Uede, S. R. Rittling, D. T. Denhardt, W. W.-Y. Kao, et al.
Corneal Wound Healing in an Osteopontin-Deficient Mouse
Invest. Ophthalmol. Vis. Sci., April 1, 2008; 49(4): 1367 - 1375.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
S. Fujita, S. Saika, W. W.-Y. Kao, K. Fujita, T. Miyamoto, K. Ikeda, Y. Nakajima, and Y. Ohnishi
Endogenous TNF{alpha} Suppression of Neovascularization in Corneal Stroma in Mice
Invest. Ophthalmol. Vis. Sci., July 1, 2007; 48(7): 3051 - 3055.
[Abstract] [Full Text] [PDF]

Home page
 Arch OphthalmolHome page
S. Saika, O. Yamanaka, I. Nishikawa-Ishida, A. Kitano, K. C. Flanders, Y. Okada, Y. Ohnishi, Y. Nakajima, and K. Ikeda
Effect of Smad7 Gene Overexpression on Transforming Growth Factor beta-Induced Retinal Pigment Fibrosis in a Proliferative Vitreoretinopathy Mouse Model
Arch Ophthalmol, May 1, 2007; 125(5): 647 - 654.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
K. Chen, Y. Wei, G. C. Sharp, and H. Braley-Mullen
Decreasing TNF-{alpha} results in less fibrosis and earlier resolution of granulomatous experimental autoimmune thyroiditis
J. Leukoc. Biol., January 1, 2007; 81(1): 306 - 314.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2006 by the American Society for Investigative Pathology.