Zymosan-Induced Murine Peritonitis Is Associated with an Increased Sphingolipid Synthesis without Changing the Long to Very Long Chain Ceramide Ratio

Abstract

Sphingolipids are key molecules in inflammation and defense against pathogens. Their role in dectin-1/TLR2-mediated responses is, however, poorly understood. This study investigated the sphingolipidome in the peritoneal fluid, peritoneal cells, plasma, and spleens of mice after intraperitoneal injection of 0.1 mg zymosan/mouse or PBS as a control. Samples were collected at 2, 4, 8, and 16 h post-injection, using a total of 36 mice. Flow cytometry analysis of peritoneal cells and measurement of IL-6, IL-1β, and TNF-α levels in the peritoneal lavages confirmed zymosan-induced peritonitis. The concentrations of sphingoid bases, dihydroceramides, ceramides, dihydrosphingomyelins, sphingomyelins, monohexosylceramides, and lactosylceramides were increased after zymosan administration, and the effects varied with the time and the matrix measured. The greatest changes occurred in peritoneal cells, followed by peritoneal fluid, at 8 h and 4 h post-injection, respectively. Analysis of the sphingolipidome suggests that zymosan increased the de novo synthesis of sphingolipids without change in the C14–C18:C20–C26 ceramide ratio. At 16 h post-injection, glycosylceramides remained higher in treated than in control mice. A minor effect of zymosan was observed in plasma, whereas sphinganine, dihydrosphingomyelins, and monohexosylceramides were significantly increased in the spleen 16 h post-injection. The consequences of the observed changes in the sphingolipidome remain to be established.

Fumonisins alone or mixed with other fusariotoxins increase the C22–24:C16 sphingolipid ratios in chickens and ducks, while deoxynivalenol and zearalenone have no effect

“…The effects of the FDZ diet measured on the concentrations of sphinganine, dihydroceramides, and dihydrosphingomyelins were greater than those observed on sphingosine, ceramides, and sphingomyelins. Greater increases in dihydrosphingolipids than sphingolipids have already been described in mice during non-infectious in ammatory peritonitis induced by zymosan administration, and by endoplasmic reticulum stress secondary to the administration of the calcium signalling modulator thapsigargin [43,44]. In ammatory effects of fusariotoxins have been reported in recent studies of fumonisins [45][46][47][48][49], deoxynivalenol [50][51][52][53][54][55] Taken together, all these results support the hypothesis that an increase in de novo synthesis of sphingolipids occurs in chickens exposed to an FDZ diet, with the difference between chickens and ducks likely being likely by the duration of the exposure, and this latter point is consistent with results obtained in turkeys [21].…”