Normal acute and chronic inflammatory responses in sphingosine kinase 1 knockout mice.
Sphingosine-1-phosophate, generated from the phosphorylation of sphingosine by sphingosine kinase enzymes, is suggested to function as an intracellular second messenger for inflammatory mediators, including formyl peptide, C5a, and Fc. More recently, a role for sphingosine kinases during inflammation has also been proposed. Here we show that sphingosine kinase 1 knockout mice exhibit normal inflammatory cell recruitment during thioglycollate-induced peritonitis and that sphingosine kinase 1-null neutrophils respond normally to formyl peptide. In the collagen-induced arthritis model of rheumatoid arthritis, sphingosine kinase 1 knockout mice developed arthritis with normal incidence and severity. Our findings show that sphingosine kinase 1 is dispensable for inflammatory responses and support the need for more extensive studies of sphingosine kinases in inflammation.
Michaud
Jason
J
Center for Vascular Biology, Department of Cell Biology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-3501, USA.
Kohno
Masataka
M
Proia
Richard L
RL
Hla
Timothy
T
D000208:Acute Disease; D000818:Animals; D001483:Base Sequence; D002908:Chronic Disease; D017931:DNA Primers; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D009504:Neutrophils / Q000201:enzymology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000099157:Sphingosine Kinase
D017931:DNA Primers; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019255:NADPH Oxidases; D017853:Phosphotransferases (Alcohol Group Acceptor); D000099157:Sphingosine Kinase