Stimulation of the ceramide pathway partially mimics lipopolysaccharide-induced responses in murine peritoneal macrophages
| Autor: | Ranney McNally, Stefanie N. Vogel, Sheila A. Barber, Gregory R. Detore |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Lipopolysaccharides
Ceramide medicine.medical_treatment Immunology Sphingomyelin phosphodiesterase Biology Ceramides Second Messenger Systems Microbiology Mice chemistry.chemical_compound Interferon Phosphoprotein Phosphatases medicine Animals Secretion Enzyme Inhibitors Oxazoles Mice Inbred C3H Tumor Necrosis Factor-alpha Macrophage Activation Molecular biology Chemokine CXCL10 Repressor Proteins Sphingomyelin Phosphodiesterase Infectious Diseases Cytokine chemistry Interferon Regulatory Factors Macrophages Peritoneal Cytokines Marine Toxins lipids (amino acids peptides and proteins) Parasitology Tumor necrosis factor alpha Cytokine secretion Interferons Carrier Proteins Sphingomyelin Chemokines CXC Research Article medicine.drug |
| Zdroj: | Infection and Immunity. 64:3397-3400 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.64.8.3397-3400.1996 |
| Popis: | Recent studies have suggested that lipolysaccharide (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-alpha) 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-alpha secretion and LPS-induced TNF-alpha 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-alpha upon secondary challenge with either LPS or SMase, whereas macrophages preexposed to SMase secreted high levels of TNF-alpha 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. |
| Databáze: | OpenAIRE |
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