TY - JOUR
T1 - Acid sphingomyelinase-derived ceramide is not required for inflammatory cytokine signalling in murine macrophages
AU - Manthey, Carl L.
AU - Schuchman, Edward H.
N1 - Funding Information:
This work was funded\ in part\ by National Institutes of Health grant HD17596 and March of Dimes Birth Defect Foundation grant 0!113[
PY - 1998/9
Y1 - 1998/9
N2 - Sphingomyelin hydrolysis is induced in myeloid cell-lines by tumour necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interferon gamma (IFN-γ). Ceramide, a product of sphingomyelin hydrolysis, recapitulates many of the cellular responses elicited by these cytokines, and this has led to the hypothesis that ceramide is a second messenger of cytokine signalling. Sphingomyelin hydrolysis is catalysed by an acid sphingomyelinase (ASMase) and one or more neutral sphingomyelinases (NSMase); both ASMase and NSMase are activated during cytokine signalling. In the present study, the contribution of ASMase to TNF-α, IL-1β, and IFN-γ signalling in murine macrophages was addressed. Cytokine-induced responses were compared in macrophages derived from the bone marrow of ASMase null and wild-type mice. Specifically, TNF-α- and IFN-γ-induced nitric oxide production and TNF-α- and IL-1β-induced expression of the α-chemokine, KC, were intact in ASMase null macrophages. Furthermore, TNF-α induction of p42/p44 ERK and p38-MAPK phosphorylation, c-jun kinase activation, and IκBα degradation were normal. Also normal in ASMase null macrophages was TNF-α-, IL-1β and IFN-γ-induced expression of a panel of early response genes. It is concluded that ASMase is non-essential for the inflammatory signals activated in murine macrophages by TNF-α, IL-1β and IFN-γ.
AB - Sphingomyelin hydrolysis is induced in myeloid cell-lines by tumour necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interferon gamma (IFN-γ). Ceramide, a product of sphingomyelin hydrolysis, recapitulates many of the cellular responses elicited by these cytokines, and this has led to the hypothesis that ceramide is a second messenger of cytokine signalling. Sphingomyelin hydrolysis is catalysed by an acid sphingomyelinase (ASMase) and one or more neutral sphingomyelinases (NSMase); both ASMase and NSMase are activated during cytokine signalling. In the present study, the contribution of ASMase to TNF-α, IL-1β, and IFN-γ signalling in murine macrophages was addressed. Cytokine-induced responses were compared in macrophages derived from the bone marrow of ASMase null and wild-type mice. Specifically, TNF-α- and IFN-γ-induced nitric oxide production and TNF-α- and IL-1β-induced expression of the α-chemokine, KC, were intact in ASMase null macrophages. Furthermore, TNF-α induction of p42/p44 ERK and p38-MAPK phosphorylation, c-jun kinase activation, and IκBα degradation were normal. Also normal in ASMase null macrophages was TNF-α-, IL-1β and IFN-γ-induced expression of a panel of early response genes. It is concluded that ASMase is non-essential for the inflammatory signals activated in murine macrophages by TNF-α, IL-1β and IFN-γ.
KW - Ceramide
KW - Interleukin 1
KW - Macrophages
KW - Signalling
KW - Sphingomyelinase
KW - Tumour necrosis factor
UR - http://www.scopus.com/inward/record.url?scp=0032168147&partnerID=8YFLogxK
U2 - 10.1006/cyto.1998.0344
DO - 10.1006/cyto.1998.0344
M3 - Article
C2 - 9770326
AN - SCOPUS:0032168147
SN - 1043-4666
VL - 10
SP - 654
EP - 661
JO - Cytokine
JF - Cytokine
IS - 9
ER -