TY - JOUR
T1 - Stimulation of the ceramide pathway partially mimics lipopolysaccharide-induced responses in murine peritoneal macrophages
AU - Barber, Sheila A.
AU - Detore, Gregory
AU - McNally, Ranney
AU - Vogel, Stefanie N.
PY - 1996
Y1 - 1996
N2 - Recent studies have suggested that lipopolysaccharide (LPS) stimulates cells by mimicking the second-messenger function of ceramide, a lipid generated in the cell by the action of sphingomyelinase (SMase). To examine this possibility further, we compared the abilities of LPS, SMase, and/or ceramide analogs to induce cytokine secretion, modulate gene expression, and induce endotoxin tolerance in macrophages. SMase and LPS induced secretion of tumor necrosis factor alpha (TNF-α) to comparable degrees; however, unlike LPS, SMase failed to stimulate detectable interferon activity. Cell- permeable analogs of ceramide induced the expression of many LPS-inducible genes; however, the expression of interferon-inducible protein 10 (IP-10) and interferon consensus sequence-binding protein (ICSBP) mRNAs was significantly lower than that induced by LPS. Both SMase-induced TNF-α secretion and LPS-induced TNF-α secretion were inhibited by pretreatment with a serine/threonine phosphatase inhibitor, calyculin A. Macrophages preexposed in vitro to LPS to induce a well-characterized state of endotoxin tolerance secreted little or no TNF-α upon secondary challenge with either LPS or SMase, whereas macrophages preexposed to SMase secreted high levels of TNF-α upon secondary stimulation with LPS or SMase. Collectively, these results suggest that ceramide activates a subset of LPS-induced signaling pathways in murine peritoneal exudate macrophages.
AB - Recent studies have suggested that lipopolysaccharide (LPS) stimulates cells by mimicking the second-messenger function of ceramide, a lipid generated in the cell by the action of sphingomyelinase (SMase). To examine this possibility further, we compared the abilities of LPS, SMase, and/or ceramide analogs to induce cytokine secretion, modulate gene expression, and induce endotoxin tolerance in macrophages. SMase and LPS induced secretion of tumor necrosis factor alpha (TNF-α) to comparable degrees; however, unlike LPS, SMase failed to stimulate detectable interferon activity. Cell- permeable analogs of ceramide induced the expression of many LPS-inducible genes; however, the expression of interferon-inducible protein 10 (IP-10) and interferon consensus sequence-binding protein (ICSBP) mRNAs was significantly lower than that induced by LPS. Both SMase-induced TNF-α secretion and LPS-induced TNF-α secretion were inhibited by pretreatment with a serine/threonine phosphatase inhibitor, calyculin A. Macrophages preexposed in vitro to LPS to induce a well-characterized state of endotoxin tolerance secreted little or no TNF-α upon secondary challenge with either LPS or SMase, whereas macrophages preexposed to SMase secreted high levels of TNF-α upon secondary stimulation with LPS or SMase. Collectively, these results suggest that ceramide activates a subset of LPS-induced signaling pathways in murine peritoneal exudate macrophages.
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M3 - Article
C2 - 8757882
AN - SCOPUS:0030037297
SN - 0019-9567
VL - 64
SP - 3397
EP - 3400
JO - Infection and Immunity
JF - Infection and Immunity
IS - 8
ER -