CXCL14/BRAK Protein, Human

The chemokine CXCL14 is a highly conserved, homeostatic chemokine which is constitutively expressed in several normal tissues including adipose, brain, breast, cervix, lung, kidney, and skin. CXCL14 is involved in infectious and inflammatory diseases, angiogenesis, and cancer^[1][2].
Among chemokines, CXCL14 is highly conserved in mammals with only two amino acids difference between mice and humans. CXCL14 has four conserved cysteine residues that form disulfide bonds7. Also, in common, the first 22 amino acids of the N-terminus are strongly hydrophobic and act as a signal peptide, which is cleaved prior to secretion. Like other chemokines, CXCL14 is a chemoattractant, especially for monocytes, and induces maturation and migration of dendritic cells (DCs). However, the CXCL14-related migration of monocyte in the absence of prostaglandin E2 (PGE2) is weak, showing that PGE2 is required for CXCL14-related chemotaxis. Responsiveness of monocytes to CXCL14 and PGE2 is specific, and B and T cells do not have any chemotactic response. In addition to monocytes, CXCL14 specifically increases chemotaxis of CD56+ natural killer (NK) cells. Responsible for immune cell recruitment and maturation, as well as impacting epithelial cell motility, CXCL14 contributes to the establishment of immune surveillance within normal epithelial layers. Overall, CXCL14 is responsible for the infiltration of immune cells, maturation of dendritic cells, upregulation of major histocompatibility complex (MHC)-I expression, and cell mobilization. Although fibroblast-derived CXCL14 has a tumor-supportive role, epithelial-derived CXCL14 mainly inhibits tumor progression^[1][2].
Many previous studies on CXCL14 have shown contradictory functions of CXCL14: tumor suppression vs. promotion, increased vs. decreased cell migration, angiogenesis vs. angiostasis, and CXCR4 inhibition vs. activation vs. no effect. CXCL14 inhibits chemotaxis of endothelial cells by directly binding to IL-8 and FGF2, thus hindering their interaction with high-affinity receptors on human vascular endothelial cells. Moreover, CXCL14 broadly modulates chemotaxis, differentiation, and activation of various types of immune cells. Furthermore, CXCL14 also shows antimicrobial activity that effectively clears infection of Streptococcus pneumoniae in respiratory tracts^[2].

Recombinant human CXCL14 (5-200 ng/mL) induced dendritic cell attraction in head and neck squamous cell carcinoma (HNSCC). CXCL14 resultes in up-regulation of the expression of dendritic cell maturation markers, as well as enhanced proliferation of allogeneic T cells in MLR. Activation of dendritic cell with recombinant human CXCL14 is accompanied by up-regulation of NF-κB activity^[3].