BIDIRECTIONAL FEEDBACK-REGULATION ON 17 KD TUMOR-NECROSIS-FACTOR (TNF) PRODUCTION BY 26 KD MEMBRANE-BOUND TNF PRECURSOR

Based on the hypothesis that 26kD membrane-bound rumor necrosis factor precursor (proTNF) may act as a principle regulator to maintain homeo stasis in an adult, we tried to examine whether proTNF shows bidirecti onal regulation in specific cellular response. We focused on productio n of 17kD mature TNF by acute monocytic leukemia cells THP-1 after sti mulation by lipopolysaccharide. ProTNF of primed THP-1 cells had been shown to act as a positive regulator for production of mature TNF by h omologous cells (primed THP-1) after LPS stimulation, whereas when THP -1 cells were co-cultivated with NIH3T3 which expressed pro-TNF, produ ction of mature TNF by THP-1 by LPS was significantly suppressed. Thes e results suggested that pro-TNF was really involved in bidirectional feedback regulation for TNF production by THP-1 cells themselves throu gh cell to cell contact. (C) 1996 WiIey-Liss, Inc.