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  • pretomanid br Materials and methods br


    Materials and methods
    Results and discussion
    Conflict of interest
    Acknowledgments This work was financially supported by the National Natural Science Foundation of China (31302162, 31171762), National High Technology Research and Development Program of China (863 Program, 2012AA101607) and China Postdoctoral Science Foundation (2013M531652).
    Introduction Chemokines are chemoattractant cytokines with roles in embryogenesis and hematopoiesis. They act to promote cell–cell adhesion, chemotaxis, cell proliferation, and directional migration of cells. They exert their effects through binding to specific G-coupled chemokine receptors located on hematopoietic pretomanid of the granulocytic lineage, monocytes, lymphocytes, and dendritic cells [1]. Receptors for some chemokines have been detected on non-hematopoietic cell types including neurons, astrocytes, epithelial cells, and endothelial cells [2], [3]. The presence of chemokine receptors on non-hematopoietic cells suggests that chemokines have roles beyond leukocyte chemotaxis. While chemokines are essential components of the immune and central nervous systems, little is known about their distribution or that of their receptors during human fetal development. One non-hematopoietic role of a chemokine has been shown in mice with targeted gene disruptions for CXCR-4 and stromal cell-derived factor 1α (SDF-1/CXCL-12) [4], [5], [6]. Mutant embryos have defects including intestinal vasculature malformations, abnormal migration of cerebellar neurons, and cardiac ventricular septal defects. Our aim in the present study was to determine whether brain, heart, intestine, liver, and kidney of normal human fetuses possessed these chemokine receptors. Such information could have potential importance in enhancing our understanding of the origin of defects in organogenesis in the human fetus as have been shown in murine models.
    Materials and methods
    Discussion Our results indicate co-expression pretomanid of CXCR-4 and SDF-1/CXCL-12 throughout gestation in each of the tissues examined. While most chemokines and receptors have overlapping binding specificity with other family members, CXCR-4 and SDF-1/CXCL12 bind only to each other. Evolutionary analysis indicates that SDF-1/CXCL-12 diverged early from other chemokines and remained conserved [9], [10].Other studies suggest that SDF-1/CXCL-12 is a unique, potentially primordial member of the chemokine family with broad developmental functions [11], [12].
    Chemokines are small proteins produced by several cell types that mediate the trafficking of immune functional cells to sites of inflammation. Chemokines thus far identified in mammals share similar 3-dimensional structure and are classified into four distinct subgroups (CXC, CC, C and CXC) based on the arrangement of their first two cysteine residues . CXCL8, a member of CXC chemokine, has also been reported in teleosts , , , , and agnatha . Unlike their mammalian counterparts, however, fish CXCL8 lacks an ELR motif, whose presence has been shown to be important in ligand/receptor interactions on mammalian neutrophils. In mammals, CXC chemokines exert effects on their target cell via different CXC receptors (CXCRs), a group of structurally related seven domain transmembrane molecules coupled with G-protein . The cDNA sequences of CXCR homolog have also been reported in fish , , , , , , although the genomic structures of these receptors in fish are as-yet unknown. The overall picture of the biology of fish chemokine and chemokine receptors is far from complete due to a paucity of basic information. Our immediate goal of this study is to develop a better understanding of the network of cell and cytokine/chemokine interactions in fish, and ultimately, to use this knowledge to more fully understand the fish immune response. For these purposes, we focused on CXCL8 and CXCRs in fugu, , whose genome sequences were previously analyzed . We (1) isolated the genes for fugu CXCL8 and two CXCRs; (2) characterized their respective genomic structures and showed their localization, and (3) measured changes in expression in their response to antigenic stimulation.