The pyrimidinergic P2Y6 receptor mediates a novel release of proinflammatory cytokines and chemokines in monocytic cells stimulated with UDP.
The human P2Y6 receptor (hP2Y6) is a member of the G protein-coupled pyrimidinergic P2 receptor family that responds specifically to the extracellular nucleotide uridine diphosphate (UDP). Recently, the hP2Y6 receptor has been reported to mediate monocyte IL-8 production in response to UDP or lipopolysaccharide (LPS), but the role of hP2Y6 in regulating other pro-inflammatory cytokines or mediators is largely unknown. We demonstrate here that UDP specifically induces soluble TNF-alpha and IL-8 production in a promonocytic U937 cell line stably transfected with hP2Y6. However, we did not detect IL-1alpha, IL-1beta, IL-6, IL-10, IL-18, and PGE2 in the conditioned media from the same cell line. These results distinguish UDP/P2Y6 signaling from LPS signaling. Interestingly, UDP induces the production of IL-8, but not TNF-alpha, in human astrocytoma 1321N1 cell lines stably transfected with hP2Y6. Therefore, the immune effect of UDP/P2Y6 signaling on the production of proinflammatory cytokines is selective and dependent on cell types. We further identify that UDP can also induce the production of proinflammatory chemokines MCP-1 and IP-10 in hP2Y6 transfected promonocytic U937 cell lines, but not astrocytoma 1321N1 cell lines stably transfected with hP2Y6. From the Taqman analysis, UDP stimulation significantly upregulates the mRNA levels of IL-8, IP-10, and IL-1beta, but not TNF-alpha. Taken together, these new findings expand the pro-inflammatory biology of UDP mediated by the P2Y6 receptor.
Cox
Mary Ann
MA
Department of Inflammation and Infection, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
Gomes
Benedict
B
Palmer
Kyle
K
Du
Karen
K
Wiekowski
Maria
M
Wilburn
Brian
B
Petro
Mary
M
Chou
Chuan-Chu
CC
Desquitado
Charlene
C
Schwarz
Martin
M
Lunn
Charles
C
Lundell
Daniel
D
Narula
Satwant K
SK
Zavodny
Paul J
PJ
Jenh
Chung-Her
CH
D001483:Base Sequence; D045744:Cell Line, Tumor; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers; D006801:Humans; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D014530:Uridine Diphosphate / Q000494:pharmacology*
D018925:Chemokines; D016207:Cytokines; D017931:DNA Primers; D012333:RNA, Messenger; D018048:Receptors, Purinergic P2; C099845:purinoceptor P2Y6; D014530:Uridine Diphosphate