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Inhibitors of protein tyrosine kinase suppress TNF-stimulated induction of endothelial cell adhesion molecules.
J Immunol. 1995 Jul 01; 155(1):445-51.JI

Abstract

We studied the role of tyrosine phosphorylation in the induction of vascular cell adhesion molecule 1 (VCAM-1), endothelial leukocyte adhesion molecule 1 (ELAM-1), and intercellular adhesion molecule 1 (ICAM-1) in HUVEC. Induction of VCAM-1 and ELAM-1 surface expression by TNF was dose-dependently reduced by pretreatment with the protein tyrosine kinase inhibitors herbimycin A (HMA, IC50 300 nM) or genistein (IC50 30 microM). Only genistein attenuated ICAM-1 induction. Genistein or HMA did not affect adhesion molecule up-regulation by PMA. U937 monocyte adhesion to TNF-stimulated HUVEC was markedly inhibited by a combination of anti-VCAM-1 and anti-ELAM-1 mAb, as well as by HMA or genistein, probably due to suppression of VCAM-1 and ELAM-1 up-regulation. HMA appeared to prevent VCAM-1 transcription, since it reduced induction of VCAM-1 mRNA by TNF. Gelshift analysis demonstrated inhibition of TNF-induced nuclear factor-kappa B (NF-kappa B) mobilization by HMA. TNF rapidly enhanced tyrosine phosphorylation of a protein migrating with an apparent molecular mass of 35 kDa. HMA and genistein suppressed constitutive tyrosine phosphorylation of all detectable proteins and prevented TNF-induced tyrosine phosphorylation of the 35 kDa protein with an IC50 and dose range, similar to inhibition of VCAM-1 and ELAM-1 induction. Our data suggest that specific phosphorylation following protein tyrosine kinase activation may be required for NF-kappa B mobilization and induction of VCAM-1 and ELAM-1 by TNF.

Authors+Show Affiliations

Institute for Cardiovascular Diseases, Ludwig Maximilians University, Munich, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7541425

Citation

Weber, C, et al. "Inhibitors of Protein Tyrosine Kinase Suppress TNF-stimulated Induction of Endothelial Cell Adhesion Molecules." Journal of Immunology (Baltimore, Md. : 1950), vol. 155, no. 1, 1995, pp. 445-51.
Weber C, Negrescu E, Erl W, et al. Inhibitors of protein tyrosine kinase suppress TNF-stimulated induction of endothelial cell adhesion molecules. J Immunol. 1995;155(1):445-51.
Weber, C., Negrescu, E., Erl, W., Pietsch, A., Frankenberger, M., Ziegler-Heitbrock, H. W., Siess, W., & Weber, P. C. (1995). Inhibitors of protein tyrosine kinase suppress TNF-stimulated induction of endothelial cell adhesion molecules. Journal of Immunology (Baltimore, Md. : 1950), 155(1), 445-51.
Weber C, et al. Inhibitors of Protein Tyrosine Kinase Suppress TNF-stimulated Induction of Endothelial Cell Adhesion Molecules. J Immunol. 1995 Jul 1;155(1):445-51. PubMed PMID: 7541425.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibitors of protein tyrosine kinase suppress TNF-stimulated induction of endothelial cell adhesion molecules. AU - Weber,C, AU - Negrescu,E, AU - Erl,W, AU - Pietsch,A, AU - Frankenberger,M, AU - Ziegler-Heitbrock,H W, AU - Siess,W, AU - Weber,P C, PY - 1995/7/1/pubmed PY - 1995/7/1/medline PY - 1995/7/1/entrez SP - 445 EP - 51 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 155 IS - 1 N2 - We studied the role of tyrosine phosphorylation in the induction of vascular cell adhesion molecule 1 (VCAM-1), endothelial leukocyte adhesion molecule 1 (ELAM-1), and intercellular adhesion molecule 1 (ICAM-1) in HUVEC. Induction of VCAM-1 and ELAM-1 surface expression by TNF was dose-dependently reduced by pretreatment with the protein tyrosine kinase inhibitors herbimycin A (HMA, IC50 300 nM) or genistein (IC50 30 microM). Only genistein attenuated ICAM-1 induction. Genistein or HMA did not affect adhesion molecule up-regulation by PMA. U937 monocyte adhesion to TNF-stimulated HUVEC was markedly inhibited by a combination of anti-VCAM-1 and anti-ELAM-1 mAb, as well as by HMA or genistein, probably due to suppression of VCAM-1 and ELAM-1 up-regulation. HMA appeared to prevent VCAM-1 transcription, since it reduced induction of VCAM-1 mRNA by TNF. Gelshift analysis demonstrated inhibition of TNF-induced nuclear factor-kappa B (NF-kappa B) mobilization by HMA. TNF rapidly enhanced tyrosine phosphorylation of a protein migrating with an apparent molecular mass of 35 kDa. HMA and genistein suppressed constitutive tyrosine phosphorylation of all detectable proteins and prevented TNF-induced tyrosine phosphorylation of the 35 kDa protein with an IC50 and dose range, similar to inhibition of VCAM-1 and ELAM-1 induction. Our data suggest that specific phosphorylation following protein tyrosine kinase activation may be required for NF-kappa B mobilization and induction of VCAM-1 and ELAM-1 by TNF. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/7541425/Inhibitors_of_protein_tyrosine_kinase_suppress_TNF_stimulated_induction_of_endothelial_cell_adhesion_molecules_ L2 - https://www.jimmunol.org/lookup/pmidlookup?view=long&pmid=7541425 DB - PRIME DP - Unbound Medicine ER -