Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prokineticin-1 (PK1) is a recently described protein with a wide range of functions, including tissue-specific angiogenesis, modulation of inflammatory responses, and regulation of hemopoiesis. The aim of this study was to investigate the localization and expression of PK1 and PK receptor-1 (PKR1), their signaling pathways, and the effect of PK1 on expression of the inflammatory mediators cyclooxygenase (COX)-2 and IL-8 in third-trimester placenta. PK1 and PKR1 were highly expressed in term placenta and immunolocalized to syncytiotrophoblasts, cytotrophoblasts, fetal endothelium, and macrophages. PK1 induced a time-dependent increase in expression of IL-8 and COX-2, which was significantly reduced by inhibitors of Gq, cSrc, epidermal growth factor receptor (EGFR), and MAPK kinase. Treatment of third-trimester placenta with 40 nm PK1 induced a rapid phosphorylation of cSrc, EGFR, and ERK1/2. Phosphorylation of ERK1/2 in response to PK1 was dependent on sequential phosphorylation of cSrc and EGFR. Using double-immunofluorescent immunohistochemistry, PKR1 colocalized with IL-8 and COX-2 in placenta. These data suggest that PK1 may have a novel role as a mediator of the inflammatory response in placenta.
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PMID:Prokineticin-1: a novel mediator of the inflammatory response in third-trimester human placenta. 1837 30

Prokineticin 1 and 2 (PROK1 and PROK2) are two small proteins largely expressed in inflammatory tissues and involved in monocyte activation and differentiation. The focus of this study was to evaluate whether PROK1 was able to induce chemokine secretion in human monocytes, in monocyte-derived macrophages and in monocyte-derived dendritic cells, an aspect not addressed thus far. Here, we show for the first time, using flow cytometry, that PROK receptors 1 and 2 are present on the surface of human monocytes. Subsequently, monocytes were selected to investigate the chemokine response after stimulation by PROK1. Our results show that only three chemokines (CCL4, CXCL1 and CXCL8) were significantly induced at both the transcript and protein level, and that PROK1 induces most potently CXCL8, in a dose-dependent manner. From a mechanistic point of view, by blocking independently Galphai protein or intracellular calcium, monocytes lose the ability to secrete CXCL8 in response to PROK1. Finally, we observed that CCL4, CXCL1 and CXCL8 secretion, following PROK1 induction, is only observed in monocytes and not in monocyte-derived macrophages and dendritic cells. Our results demonstrate that, in vitro, the differentiation status of monocytes influences chemokine production after stimulation by PROK1, and that this chemokine production is geared toward a pro-inflammatory response. This could represent a novel amplification loop of leukocyte recruitment, extravasation and tissue invasion.
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PMID:Prokineticin 1 induces CCL4, CXCL1 and CXCL8 in human monocytes but not in macrophages and dendritic cells. 1910 22