Dilinoleoylphosphatidylcholine selectively modulates lipopolysaccharide-induced Kupffer cell activation.
Polyenylphosphatidylcholine (PPC), a mixture of polyunsaturated phosphatidylcholines extracted from soybeans, protects against alcoholic and non-alcoholic liver injury. Because Kupffer cells mediate liver injury, we hypothesized that PPC may modulate their activation. The activation of Kupffer cells by lipopolysaccharide (LPS) leads to an enhanced production of cytokines. Among these, tumor necrosis factor-alpha(TNF-alpha) exerts mainly a hepatotoxic effect, whereas interleukin-1beta (IL-1beta) appears to be hepatoprotective. The present study evaluated whether dilinoleoylphosphatidylcholine (DLPC), the main component of PPC (40% to 52%), affects LPS-induced Kupffer cell activation in vitro. For comparison, palmitoyl-linoleoylphosphatidylcholine (PLPC), the other major component of PPC (23% to 24%), and distearoylphosphatidylcholine (DSPC), the saturated counterpart of DLPC, were also tested. Rat Kupffer cells were cultured in serum-free RPMI-1640 medium containing 10 micromol/L of either DLPC, PLPC, or DSPC in the presence or absence of LPS (1 microg/mL). After 20 hours in culture, the media were collected for cytokine measurements by enzyme-linked immunosorbent assays. LPS significantly stimulated TNF-alpha and IL-1beta production by 62% and 328%, respectively. Treatment of Kupffer cells with LPS plus DLPC decreased the production of TNF-alpha by 23% (12.17+/-1.83 pg/ng DNA vs 15.72 +/-2.74 pg/ng DNA, P < .05, n = 6) and increased that of IL-1beta by 17% (1.80 +/- 0.16 pg/ng DNA vs 1.54 +/- 0.08 pg/ng DNA, P< .05, n = 6). No effect of PLPC or DSPC on LPS-induced TNF-alpha or IL-1beta generation was observed, thereby illustrating the selective effect of DLPC in this process. Thus DLPC selectively modulates the LPS-induced activation of Kupffer cells by decreasing the production of the cytotoxic TNF-alpha while increasing that of the protective IL-1beta. This dual action of DLPC on cytokines may provide a mechanism for the protective effect against liver injury, but its significance still needs to be determined by in vivo studies.
Oneta
C M
CM
Alcohol Research and Treatment Center, Bronx Veterans Affairs Medical Center, NY 10468, USA.
Mak
K M
KM
Lieber
C S
CS
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis; D007728:Kupffer Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000293:injuries; D008108:Liver Diseases, Alcoholic / Q000517:prevention & control; D008297:Male; D010713:Phosphatidylcholines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D007375:Interleukin-1; D008070:Lipopolysaccharides; D010713:Phosphatidylcholines; D014409:Tumor Necrosis Factor-alpha; C002448:1,2-linoleoylphosphatidylcholine; C010942:1,2-distearoyllecithin