| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
American Journal of Pathology, Vol 149, 195-204, Copyright © 1996 by American Society for Investigative Pathology
REGULAR ARTICLES |
M Buck, K Houglum and M Chojkier
Department of Medicine, Veterans Affairs Medical Center, San Diego, California, USA.
The mechanisms responsible for impaired wound healing in patients with cachexia-associated infection, inflammation, and cancer are unknown. As tumor necrosis factor (TNF)-alpha is elevated in these diseases, and TNF-alpha inhibits collagen alpha1(I) gene expression in cultured fibroblasts, we analyzed whether chronically elevated serum TNF-alpha affects collagen metabolism in vivo by inoculating nude mice with Chinese hamster ovary cells secreting TNF-alpha (TNF-alpha mice) or control Chinese hamster ovary cells (control mice). Before the onset of weight loss, TNF-alpha mice had a selective decrease in collagen synthesis and collagen alpha1(I) mRNA in the skin. In addition, TNF- alpha mice displayed impaired healing of incisional and excisional skin wounds, compared with control animals, before the onset of cachexia. The expression of transforming growth factor-beta1, a potent fibrogenic factor, was inhibited by TNF-alpha in the skin. In studies with transgenic mice expressing the human growth hormone under the direction of 5' regulatory regions of the human collagen alpha1(I) gene, TNF- alpha treatment inhibited the expression of the collagen alpha1(I) human growth hormone transgene containing -2.3 kb of the 5' region, whereas transgene expression directed by -0.44 kb of the 5' region was not affected. These experiments suggest that TNF-alpha may play an important role in the impaired wound healing of chronic diseases that are characterized by a high production of this cytokine and provide insights for potential therapeutic approaches.
This article has been cited by other articles:
 |
|
 |
|
  T. Yukami, M. Hasegawa, Y. Matsushita, T. Fujita, T. Matsushita, M. Horikawa, K. Komura, K. Yanaba, Y. Hamaguchi, T. Nagaoka, et al. Endothelial selectins regulate skin wound healing in cooperation with L-selectin and ICAM-1 J. Leukoc. Biol., September 1, 2007; 82(3): 519 - 531. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Mehl, J. M. Davis, F. G. Berger, and J. A. Carson Myofiber degeneration/regeneration is induced in the cachectic ApcMin/+ mouse J Appl Physiol, December 1, 2005; 99(6): 2379 - 2387. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Alikhani, Z. Alikhani, H. He, R. Liu, B. I. Popek, and D. T. Graves Lipopolysaccharides Indirectly Stimulate Apoptosis and Global Induction of Apoptotic Genes in Fibroblasts J. Biol. Chem., December 26, 2003; 278(52): 52901 - 52908. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. MORI, T. KONDO, T. OHSHIMA, Y. ISHIDA, and N. MUKAIDA Accelerated wound healing in tumor necrosis factor receptor p55-deficient mice with reduced leukocyte infiltration FASEB J, July 1, 2002; 16(9): 963 - 974. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H Gardner, A Broberg, A Pozzi, M Laato, and J Heino Absence of integrin alpha1beta1 in the mouse causes loss of feedback regulation of collagen synthesis in normal and wounded dermis J. Cell Sci., January 2, 1999; 112(3): 263 - 272. [Abstract] [PDF]
|
|
|
|
 |
|
 M. Chojkier, K. Houglum, K. S. Lee, and M. Buck Long- and short-term D-alpha -tocopherol supplementation inhibits liver collagen alpha 1(I) gene expression Am J Physiol Gastrointest Liver Physiol, December 1, 1998; 275(6): G1480 - G1485. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Houglum, M. Buck, D. J. Kim, and M. Chojkier TNF-alpha inhibits liver collagen-alpha 1(I) gene expression through a tissue-specific regulatory region Am J Physiol Gastrointest Liver Physiol, May 1, 1998; 274(5): G840 - G847. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
