S-form lipopolysacchavide (LPS), but not lipid A or R-chemo-type LPS, induces interleukin-6 production in vitamin D-3 differentiated THP-1 cells

Bacterial lipopolysaccharide (LPS) induces the production of various inflam matory cytokines and the inducibility is considered attributable to the gly colipid part of LPS called lipid A. We report an in vitro model in which li pid A is not necessarily a minimal structure for the LPS activity, Vitamin D-3-differentiated THP-1 cells, cultured human monocytic leukemia cells, pr oduced a high level of interleukin-6 (IL-6) by stimulating LPS from Escheri chia coli O111:B4, but not by stimulating synthetic E. coli-type lipid A (c ompound 506), E. coli Re mutant LPS (ReLPS), or alkali-treated LPS, The ind uction by LPS was inhibited by the anti-CD14 antibodies or by the synthetic lipid A precursor (compound 406), An alkali-treated LPS or compound 506 pa rtially inhibited the LPS-induced IL-6 production. These facts suggest that lipid A alone is not sufficient for the IL-6-inducing activity, but the po lysaccharide part in LPS contributes or acts as a co-factor for activation of differentiated THP-1 cells. (C) 1999 Academic Press.