Reduced inflammatory potential of peritoneal macrophages recruited in mice pretreated with a glycolipid synthesis inhibitor

• Published in: Inflammopharmacology Vol. 14; no. 3-4; pp. 170 - 160
• Main Authors: Yohe, H C, Kitzmiller, T J, Bement, W J, Dwyer, B E, Sinclair, J F
• Format: Journal Article
• Language: English
• Published: Switzerland 01-08-2006
• Subjects: 1-Deoxynojirimycin - analogs & derivatives; Animals; Cell Survival - drug effects; Cytokines - metabolism; Enzyme Inhibitors - pharmacology; Glucosamine - analogs & derivatives; Glucosamine - pharmacology; Glucosyltransferases - antagonists & inhibitors; Glycosphingolipids - antagonists & inhibitors; Glycosphingolipids - biosynthesis; Immunity, Innate - drug effects; Macrophages, Peritoneal - drug effects; Macrophages, Peritoneal - enzymology; Macrophages, Peritoneal - immunology; Macrophages, Peritoneal - metabolism; Mice; Mice, Inbred C3H
• ISSN: 0925-4692; 1568-5608
• DOI: 10.1007/s10787-006-1517-5

Integral components of mammalian cell membranes, glycosphingolipids (GSL) reside in specialized plasma membrane microdomains critical for cell signaling. N-alkylated nojirimycins are compounds developed for GSL substrate deprivation therapy, blocking GSL synthesis by specifically inhibiting an essential enzyme, ceramide glucosyltransferase. Peritoneal macrophages recruited in mice pretreated with an inhibitory N-alkylnojirimycin displayed a reduced capacity to release either TNFalpha or interleukin-6 when re-exposed to whole killed E. coli in vitro. Cell viability and protein content were not affected. A nojirimycin analogue without GSL inhibitory capacity had no effect. The results show inhibition of GSL synthesis in vivo by an N-alkylnojirimycin can reduce the response to an inflammatory stimulus and indicate N-alkylnojirimycins have experimental and potential clinical value for modulating innate immune responses in vivo.