Anti-XCL1 polyclonal antibody

ProblemCertain chemokines with their receptors can promote or inhibit trophoblast cell migration and invasion in human first-trimester placenta. Whether the lymphotactin (Lptn; XCL1)XC chemokine receptor 1 (XCR1) chemokine pathway affects trophoblast cell migration and invasion in human first-trimester placenta remains unclear. Method of studyThe expression pattern of chemokine XCL1 and its receptor XCR1 was detected in human first-trimester by qRT-PCR, and the effect of recombinant human XCL1 (rhXCL1) on trophoblast cell function was tested by wound healing and Transwell assays. Matrix metalloproteinase (MMP) activity in trophoblast cells treated with rhXCL1 was assessed via qRT-PCR and gelatin zymography. ResultsAbundant XCR1 mRNA was expressed in the first-trimester decidua and villi. XCL1 and XCR1 mRNA were expressed at a higher level in the first-trimester than in the term placenta. RhXCL1 promoted trophoblast cell migration and invasion by increasing MMP-9 and MMP-2 activity and that of the MMP-2/tissue inhibitor of metalloproteinases 2 (TIMP-2) complex via the phosphatidylinositol 3-kinase (PI3K)/AKT kinase (AKT), mitogen-activated protein kinase (MEK), and JUN N-terminal kinase (JNK) signaling pathways. ConclusionXCL1-XCR1 chemokine pathway promotes trophoblast invasion by increasing matrix metalloproteinase activity in human first-trimester placenta.

Human herpesvirus-6A (HHV-6A) betachemokine-receptor U51A binds inflammatory modulators CCL2, CCL5, CCL11, CCL7, and CCL13. This unique specificity overlaps that of human chemokine receptors CCR1, CCR2, CCR3, and CCR5. In model cell lines, expression leads to CCL5 down-regulation with both constitutive and inducible signaling. Here, immunomodulation pathways are investigated in human leukocytes permissive for infection. Constitutive signaling was shown using inositol phosphate assays and inducible calcium signaling by response to CCL2, CCL5 and CCL11. Constitutive signaling targets were examined using an immune response-related microarray and RT-PCR, showing down-regulation of CCL5 and FOG-2, a hematopoietic transcriptional repressor. By RT-PCR and siRNA reversion, CCL5 and FOG-2 were shown down-regulated, during peak U51A expression post infection. Two further active ligands, XCL1 and CCL19, were identified, making U51A competitor to their human receptors, XCR1 and CCR7, on T lymphocytes, NK and dendritic cells. Finally, U51A-expressing cell lines and infected ex vivo leukocytes, showed migration towards chemokine-gradients, and chemokine internalization. Consequently, U51A may affect virus dissemination or host transmission by chemotaxis of infected cells to sites of chemokine secretion specific for U51A (for example the lymph node or lung, by CCL19 or CCL11, respectively) and evade immune-effector cells by chemokine diversion and down-regulation, affecting virus spread and inflammatory pathology.