The mRNA level of Charcot-Leyden crystal protein/galectin-10 is a marker for CRTH2 activation in human whole blood in vitro.
CRTH2 is one of the prostaglandin D₂ receptors and plays a proinflammatory role in allergic diseases. Gene expression markers in whole blood induced by CRTH2 activation have not previously been reported. Using microarray analyses of 54 675 genes, we revealed modest gene expression changes in human whole blood stimulated in vitro by a selective CRTH2 agonist, DK-PGD₂. Five genes were found to exhibit 1.5- to 2.6-fold changes in expression. The expression of Charcot-Leyden crystal protein/galectin-10 (CLC/Gal-10) in particular was consistently enhanced in human whole blood stimulated by DK-PGD₂, as confirmed by quantitative real-time polymerase chain reaction analyses. DK-PGD(2)-induced increases in blood CLC/Gal-10 mRNA levels were largely attenuated by the CRTH2 antagonist CAY10471.Thus, the DK-PGD₂-induced CLC/Gal-10 mRNA level can serve as a potential marker for monitoring pharmacodynamic effects of blood exposure to CRTH2 modulating agents.
Lin
Tai-An
TA
Pharma Research and Early Development, Hoffmann-La Roche Inc., Nutley, NJ 07110, USA. tai-an.lin@roche.com
Kourteva
Galina
G
Hilton
Holly
H
Li
Hongli
H
Tare
Nadine S
NS
Carvajal
Valerie
V
Hang
Julie S
JS
Wei
Xin
X
Renzetti
Louis M
LM
D001483:Base Sequence; D015415:Biomarkers / Q000378:metabolism*; D017931:DNA Primers; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D008245:Lysophospholipase / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics*; D011971:Receptors, Immunologic / Q000097:blood*; D011982:Receptors, Prostaglandin / Q000097:blood*
D015415:Biomarkers; D017931:DNA Primers; D006023:Glycoproteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D008245:Lysophospholipase; C011711:lysolecithin acylhydrolase; C036293:prostaglandin D2 receptor