PMID- 1335785 OWN - NLM STAT- MEDLINE DCOM- 19930205 LR - 20181130 IS - 0956-960X (Print) IS - 0956-960X (Linking) VI - 3 IP - 4 DP - 1992 Oct TI - Protein kinase C regulates secretion of lymphotoxin (LT/TNF beta) and TNF alpha by human EBV-transformed B cells. PG - 162-7 AB - Epstein-Barr virus (EBV)-transformed cell lines constitutively secrete lymphotoxin (LT/TNF beta) and not tumor necrosis factor-alpha (TNF alpha). To analyze the cellular processes that regulate LT and TNF alpha secretion by lymphoblastoid cell lines, we studied the role of two signal transduction pathways leading to either protein kinase C (PK-C) or PK-A activation. We demonstrate that PK-C activation, either after cross-linking of surface Ig or by direct activation with phorbolester, leads to increased production of both LT and TNF alpha, whereas no prominent role for PK-A was found. Interleukin (Il)-4 was found to synergize with PK-C activation in raising levels of secreted LT and TNF alpha. Increased levels of LT and TNF alpha did not correlate with augmented levels of immunoglobulin secreted by the cell lines nor with improved proliferation. These observations demonstrate that EBV B cells respond to B cell activation signals leading to PK-C activation with increased production of both LT and TNF alpha. It is, however, unlikely that these molecules serve as autostimulatory factors for EBV B cells, but in contrast might play a role in downregulation of biological functions in these cells. FAU - Jochems, G J AU - Jochems GJ AD - Department of Clinical (Viro-)Immunology, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam. FAU - Klein, M R AU - Klein MR FAU - Zeijlemaker, W P AU - Zeijlemaker WP FAU - van Lier, R A AU - van Lier RA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Hum Antibodies Hybridomas JT - Human antibodies and hybridomas JID - 9014461 RN - 0 (Lymphotoxin-alpha) RN - 0 (Phosphatidylinositol 4,5-Diphosphate) RN - 0 (Phosphatidylinositols) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 2.7.- (Protein Kinases) RN - EC 2.7.11.13 (Protein Kinase C) SB - IM MH - B-Lymphocytes/immunology/*physiology MH - Cell Line, Transformed MH - Herpesvirus 4, Human MH - Humans MH - Lymphocyte Activation MH - Lymphotoxin-alpha/*metabolism MH - Phosphatidylinositol 4,5-Diphosphate MH - Phosphatidylinositols/metabolism MH - Protein Kinase C/*physiology MH - Protein Kinases/physiology MH - Signal Transduction MH - Tumor Necrosis Factor-alpha/*metabolism EDAT- 1992/10/01 00:00 MHDA- 1992/10/01 00:01 CRDT- 1992/10/01 00:00 PHST- 1992/10/01 00:00 [pubmed] PHST- 1992/10/01 00:01 [medline] PHST- 1992/10/01 00:00 [entrez] PST - ppublish SO - Hum Antibodies Hybridomas. 1992 Oct;3(4):162-7.