Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have recently identified a peptide derived from the secreted portion of the HSV-2 glycoprotein G, gG-2p20, to be proinflammatory. Based on its ability to activate neutrophils and monocytes via the formyl peptide receptor (FPR) to produce reactive oxygen species (ROS) that down-regulate NK cell function, we suggested it to be of importance in HSV-2 pathogenesis. We now describe the effects of an overlapping peptide, gG-2p19, derived from the same HSV-2 protein. Also, this peptide activated the ROS-generating NADPH-oxidase, however, only in monocytes and not in neutrophils. Surprisingly, gG-2p19 did not induce a chemotactic response in the affected monocytes despite using a pertussis toxin-sensitive, supposedly G-protein-coupled receptor. The specificity for monocytes suggested that FPR and its homologue FPR like-1 (FPRL1) did not function as receptors for gG-2p19, and this was also experimentally confirmed. Surprisingly, the monocyte-specific FPR homologue FPRL2 was not involved either, and the responsible receptor thus remains unknown so far. However, the receptor shares some basic signaling properties with FPRL1 in that the gG-2p19-induced response was inhibited by PBP10, a peptide that has earlier been shown to selectively inhibit FPRL1-triggered responses. We conclude that secretion and subsequent degradation of the HSV-2 glycoprotein G can generate several peptides that activate phagocytes through different receptors, and with different cellular specificities, to generate ROS with immunomodulatory properties.
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PMID:A monocyte-specific peptide from herpes simplex virus type 2 glycoprotein G activates the NADPH-oxidase but not chemotaxis through a G-protein-coupled receptor distinct from the members of the formyl peptide receptor family. 1794 82

The human formyl-peptide receptor (FPR) and its variants FPRL1 and FPRL2 belong to the G-protein coupled seven transmembrane receptor (GPCR) family sensitive to pertussis toxin. FPR and FPRL1 were first detected in phagocytic leukocytes, and FPRL2 was found in monocytes and in dendritic cells. The three receptors were subsequently identified in other cell types or tissues, including neuronal cells and brain, where FPR and FPRL1 play a key role in angiogenesis, cell proliferation, protection against and cell death, as well as in neuroendocrine functions. Binding of different agonists to FPRs triggers several signaling pathways, activates NFkB and STAT3 transcriptional factors and induces the accumulation of the CDK inhibitors p21(waf1/cip1), p16(INK4) and p27(kip1). Signaling molecules, such as ERKs, JNK, PKC, p38MAPK, PLC and PLD are involved in these intracellular cascades. In this article we briefly review FPRs expression and signaling in neuronal cells.
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PMID:Expression and signaling of formyl-peptide receptors in the brain. 2104 51