1. Selective up-regulation of tumor necrosis factor receptor I in tumor-bearing rats with cancer-related cachexia.
- Author
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Catalano MG, Fortunati N, Arena K, Costelli P, Aragno M, Danni O, and Boccuzzi G
- Subjects
- Animals, Antigens, CD genetics, Cachexia etiology, Interleukin-6 metabolism, Male, Neoplasms, Experimental complications, Neoplasms, Experimental pathology, RNA, Messenger genetics, RNA, Neoplasm genetics, Rats, Receptors, Interleukin-7 metabolism, Receptors, Tumor Necrosis Factor genetics, Receptors, Tumor Necrosis Factor, Type I, Receptors, Tumor Necrosis Factor, Type II, Reverse Transcriptase Polymerase Chain Reaction, Tissue Distribution, Tumor Necrosis Factor-alpha metabolism, Up-Regulation, Antigens, CD metabolism, Cachexia metabolism, Neoplasms, Experimental metabolism, Receptors, Tumor Necrosis Factor metabolism
- Abstract
Tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6) are important mediators in cancer cachexia; however, the expression of these cytokines and their receptors in tumor-bearing animals is poorly characterized. We analyzed expression of TNF-alpha, IL-6, tumor necrosis factor (TNF-RI, TNF-RII) and interleukin 6 (IL-6R) receptors in the brain, kidney, spleen, liver, muscle, ascite tumors and serum, from Yoshida AH-130 hepatoma-bearing rats. TNF-alpha increased in the brain, spleen, liver, and muscle of cachectic animals; IL-6 increased in the liver and muscle. AH-130 cells expressed a good level of TNF-alpha; on the contrary, no TNF-alpha or IL-6 protein was detected in the serum of either tumor-bearing or control animals. TNF-RI mRNA was up-regulated in the spleen, liver and muscle of tumor-bearing rats. TNF-RI protein levels confirmed up-regulation in the spleen and liver, but failed to detect any increase in the muscle. Western blotting against TNF-RI revealed two bands of lower molecular weight in cachectic muscle, suggesting proteolysis involving TNF-RI. No significant increase of either TNF-RII or IL-6R was observed. This is the first demonstration of a selective up-regulation of TNF-RI in cancer cachexia and suggests that local production of TNF-alpha and IL-6 is a corner-stone in the induction/maintenance of this syndrome.
- Published
- 2003