TY - JOUR
T1 - Cellular activation induced by BCG is a PTK-dependent event
AU - Méndez-Samperio, Patricia
AU - Hernandez-Garay, Marisol
AU - Vazquez, Angela Nuñez
N1 - Funding Information:
We gratefully acknowledge Dr. J. Ruiz-Puente for kindly supplying BCG. This research was supported in part by Grant 3367 M from the Consejo Nacional de Ciencias y Tecnologia (CONACYT) and in part by Grant 953229-1323 from the DireccioÂn de Estudios de Pos-grado e InvestigacioÂn (DEPI).
PY - 1996/7/10
Y1 - 1996/7/10
N2 - Mycobacterial antigens including BCG stimulate human peripheral blood mononuclear cells resulting in cellular proliferation and the release of inflammatory cytokines such as TNF-α. However, the signal transduction mechanisms responsible for the BCG-induced cell activation are not completely understood. In this study, we investigated the role of PTK as a signal transduction pathway in BCG-induced cell activation, with the use of two PTK inhibitors (genistein and tyrphostin). Our results indicated that genistein significantly inhibited BCG-induced cell growth determined by thymidine uptake in a dose-dependent manner. BCG-induced TNF-α secretion was completely suppressed by genistein in a dose-dependent manner, producing 92% inhibition at a concentration of 50 μM. In addition, strong inhibition (81%) of BCG-induced TNF-α secretion was observed with tyrphostin (30 μM), another specific protein tyrosine kinase with a different mechanism of action. These inhibitory effects were not attributed to an alteration in cell viability as judged by trypan blue staining, and were not due to LPS contamination. On the other hand, monoclonal antibodies directed against HLA-DR and DQ inhibited the BCG-induced secretion of TNF-α. Taken together, these findings suggest that PTK may play an essential role in BCG-induced cellular activation.
AB - Mycobacterial antigens including BCG stimulate human peripheral blood mononuclear cells resulting in cellular proliferation and the release of inflammatory cytokines such as TNF-α. However, the signal transduction mechanisms responsible for the BCG-induced cell activation are not completely understood. In this study, we investigated the role of PTK as a signal transduction pathway in BCG-induced cell activation, with the use of two PTK inhibitors (genistein and tyrphostin). Our results indicated that genistein significantly inhibited BCG-induced cell growth determined by thymidine uptake in a dose-dependent manner. BCG-induced TNF-α secretion was completely suppressed by genistein in a dose-dependent manner, producing 92% inhibition at a concentration of 50 μM. In addition, strong inhibition (81%) of BCG-induced TNF-α secretion was observed with tyrphostin (30 μM), another specific protein tyrosine kinase with a different mechanism of action. These inhibitory effects were not attributed to an alteration in cell viability as judged by trypan blue staining, and were not due to LPS contamination. On the other hand, monoclonal antibodies directed against HLA-DR and DQ inhibited the BCG-induced secretion of TNF-α. Taken together, these findings suggest that PTK may play an essential role in BCG-induced cellular activation.
UR - http://www.scopus.com/inward/record.url?scp=0030578391&partnerID=8YFLogxK
U2 - 10.1006/cimm.1996.0185
DO - 10.1006/cimm.1996.0185
M3 - Artículo
SN - 0008-8749
VL - 171
SP - 147
EP - 152
JO - Cellular Immunology
JF - Cellular Immunology
IS - 1
ER -