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Publication : Differential responses of fibroblasts from wild-type and TNF-R55-deficient mice to mouse and human TNF-alpha activation.

First Author  Mackay F Year  1994
Journal  J Immunol Volume  153
Issue  11 Pages  5274-84
PubMed ID  7525730 Mgi Jnum  J:21648
Mgi Id  MGI:69579 Doi  10.4049/jimmunol.153.11.5274
Citation  Mackay F, et al. (1994) Differential responses of fibroblasts from wild-type and TNF-R55-deficient mice to mouse and human TNF-alpha activation. J Immunol 153(11):5274-84
abstractText  The role of the two TNF receptor types, TNF-R55 and TNF-R75, was studied on mouse fibroblasts, taking advantage of TNF-R55-deficient mice generated by gene targeting (Tnfr1 degree-mice), and selectivity of human TNF-alpha for mouse TNF-R55. Radioligand binding assays showed that both TNF receptors were expressed on wild-type mouse fibroblasts, whereas normal levels of TNF-R75 were expressed on mouse fibroblasts isolated from Tnfr1 degree-mice. It was found that TNF-R55 controlled four major TNF-induced fibroblast functions: (1) adhesion to leukocyte cell lines as well as ICAM-1, VCAM-1, CD44, and MHC class I up-regulation; (2) secretion of other cytokines as demonstrated by stimulated IL-6 and granulocyte-macrophage-CSF releases; (3) cell proliferation; and (4) NF-kappa B activation. Stimulation through TNF-R75, in TNF-R55-deficient fibroblasts, did not have any effect in these functions. In general, mouse TNF-alpha (recognizing both mouse TNF receptors) had a higher sp. act. than human TNF-alpha (recognizing only mouse TNF-R55) in wild-type fibroblasts, whereas both mouse and human TNF-alpha had similar cytotoxic activities in WEHI 164 cells.
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