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Gene Review

CXCL16  -  chemokine (C-X-C motif) ligand 16

Homo sapiens

Synonyms: C-X-C motif chemokine 16, CXCLG16, SCYB16, SR-PSOX, SRPSOX, ...
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Disease relevance of CXCL16


High impact information on CXCL16


Biological context of CXCL16

  • CXCL16 signals via Gi, phosphatidylinositol 3-kinase, Akt, I kappa B kinase, and nuclear factor-kappa B and induces cell-cell adhesion and aortic smooth muscle cell proliferation [2].
  • CXCL16 induced I kappa B phosphorylation and degradation [2].
  • To dissect the biological and signal transduction pathways elicited by CXCL16, human aortic smooth muscle cells (HASMC) were treated with pharmacological inhibitors or transiently transfected with pathway-specific dominant-negative or kinase-dead expression vectors prior to the addition of CXCL16 [2].
  • By transfection of human and murine CXCL16 in different cell lines, we show that soluble CXCL16 is constitutively generated by proteolytic cleavage of transmembrane CXCL16 resulting in reduced surface expression of the transmembrane molecule [10].
  • CONCLUSION: The findings from this study have demonstrated for the first time that CXCR6 and CXCL16 are co-expressed by first-trimester human trophoblast cells and stimulate their proliferation and invasion in an autocrine/paracrine manner [11].

Anatomical context of CXCL16

  • CXCL16 was also found in the thymic medulla and in some nonlymphoid tissues, indicating roles in thymocyte development and effector T cell trafficking [7].
  • CXCL16 is expressed on the surface of APCs including subsets of CD19(+) B cells and CD14(+) monocyte/macrophages, and functional CXCL16 is also shed from macrophages [12].
  • CXCR6 may also contribute to tissue localization of plasma cells through its direct binding to membrane-anchored CXCL16 [13].
  • In vitro polarized T cell subsets including Th1, Th2, and Tr1 cells express functional Bonzo, suggesting expression of this receptor in chronic inflammation, which we further verified by demonstration of CXCL16-mediated migration of tonsil-derived CD4(+) T lymphocytes [12].
  • CXCL16 is continuously released from glial cells by proteolytic cleavage which is rapidly enhanced by stimulation with phorbol-12-myristate-13-acetate (PMA) [1].

Associations of CXCL16 with chemical compounds

  • All-trans retinoic acid regulates CXCL16/SR-PSOX expression [14].
  • These findings suggest that retinoid signaling might be a pathway modulating inflammatory response by regulating CXCL16 expression in a cell-specific manner [14].
  • Six genes were selected for confirmation by real-time PCR, and of these, CXCL16, ZNF331, JUN, and PF4 were the most significantly affected by benzene exposure, a finding that was confirmed in a larger data set from 28 subjects [15].
  • CXCL16 is a unique chemokine with characteristics as a receptor for phosphatidylserine and oxidized low density lipoproteins in macrophages, and is involved in the accumulation of cellular cholesterol during atherosclerotic lesion development [16].
  • While bacterial lipopolysaccharide (LPS) has been shown to stimulate CXCL16 expression in SMC, its effects on CXCR6 are not known [17].

Physical interactions of CXCL16

  • CXCL16 on the cholangiocyte membrane was able to support lymphocyte adhesion by triggering conformational activation of beta(1) integrins and binding to VCAM-1 [18].

Regulatory relationships of CXCL16


Other interactions of CXCL16

  • As shown by inhibitor studies, two distinct members of the disintegrin-like metalloproteinase family ADAM10 and 17 are involved in the constitutive and PMA-induced shedding of glial CXCL16 [1].
  • In addition, the constitutive cleavage of transfected human CXCL16 was markedly reduced in embryonic fibroblasts generated from ADAM10-deficient mice [10].
  • Exposure of HASMC to CXCL16 increased NF-kappa B DNA binding activity, induced kappa B-driven luciferase activity, and up-regulated tumor necrosis factor-alpha expression in an NF-kappa B-dependent manner [2].
  • The IFN-gamma induction of CXCL16 was also associated with increased uptake of oxLDL into these cells [19].
  • RESULTS: CXCL16 was markedly elevated in RA synovial fluid (SF) samples, being as high as 145 ng/ml [8].

Analytical, diagnostic and therapeutic context of CXCL16


  1. Enhanced expression and shedding of the transmembrane chemokine CXCL16 by reactive astrocytes and glioma cells. Ludwig, A., Schulte, A., Schnack, C., Hundhausen, C., Reiss, K., Brodway, N., Held-Feindt, J., Mentlein, R. J. Neurochem. (2005) [Pubmed]
  2. CXCL16 signals via Gi, phosphatidylinositol 3-kinase, Akt, I kappa B kinase, and nuclear factor-kappa B and induces cell-cell adhesion and aortic smooth muscle cell proliferation. Chandrasekar, B., Bysani, S., Mummidi, S. J. Biol. Chem. (2004) [Pubmed]
  3. Cutting edge: SR-PSOX/CXC chemokine ligand 16 mediates bacterial phagocytosis by APCs through its chemokine domain. Shimaoka, T., Nakayama, T., Kume, N., Takahashi, S., Yamaguchi, J., Minami, M., Hayashida, K., Kita, T., Ohsumi, J., Yoshie, O., Yonehara, S. J. Immunol. (2003) [Pubmed]
  4. CXCL16 is a marker of inflammation, atherosclerosis, and acute coronary syndromes in humans. Lehrke, M., Millington, S.C., Lefterova, M., Cumaranatunge, R.G., Szapary, P., Wilensky, R., Rader, D.J., Lazar, M.A., Reilly, M.P. J. Am. Coll. Cardiol. (2007) [Pubmed]
  5. Excreted urinary mediators in an animal model of experimental immune nephritis with potential pathogenic significance. Wu, T., Xie, C., Bhaskarabhatla, M., Yan, M., Leone, A., Chen, S.S., Zhou, X.J., Putterman, C., Mohan, C. Arthritis Rheum. (2007) [Pubmed]
  6. Overexpression of CXCL16 and its receptor CXCR6/Bonzo promotes growth of human schwannomas. Held-Feindt, J., Rehmke, B., Mentlein, R., Hattermann, K., Knerlich, F., Hugo, H.H., Ludwig, A., Mehdorn, H.M. Glia (2008) [Pubmed]
  7. A transmembrane CXC chemokine is a ligand for HIV-coreceptor Bonzo. Matloubian, M., David, A., Engel, S., Ryan, J.E., Cyster, J.G. Nat. Immunol. (2000) [Pubmed]
  8. CXCL16-mediated cell recruitment to rheumatoid arthritis synovial tissue and murine lymph nodes is dependent upon the MAPK pathway. Ruth, J.H., Haas, C.S., Park, C.C., Amin, M.A., Martinez, R.J., Haines, G.K., Shahrara, S., Campbell, P.L., Koch, A.E. Arthritis Rheum. (2006) [Pubmed]
  9. Pathogenic role of the CXCL16-CXCR6 pathway in rheumatoid arthritis. Nanki, T., Shimaoka, T., Hayashida, K., Taniguchi, K., Yonehara, S., Miyasaka, N. Arthritis Rheum. (2005) [Pubmed]
  10. The transmembrane CXC-chemokine ligand 16 is induced by IFN-gamma and TNF-alpha and shed by the activity of the disintegrin-like metalloproteinase ADAM10. Abel, S., Hundhausen, C., Mentlein, R., Schulte, A., Berkhout, T.A., Broadway, N., Hartmann, D., Sedlacek, R., Dietrich, S., Muetze, B., Schuster, B., Kallen, K.J., Saftig, P., Rose-John, S., Ludwig, A. J. Immunol. (2004) [Pubmed]
  11. Chemokine CXCL16, a scavenger receptor, induces proliferation and invasion of first-trimester human trophoblast cells in an autocrine manner. Huang, Y., Zhu, X.Y., Du, M.R., Wu, X., Wang, M.Y., Li, D.J. Hum. Reprod. (2006) [Pubmed]
  12. Expression cloning of the STRL33/BONZO/TYMSTRligand reveals elements of CC, CXC, and CX3C chemokines. Wilbanks, A., Zondlo, S.C., Murphy, K., Mak, S., Soler, D., Langdon, P., Andrew, D.P., Wu, L., Briskin, M. J. Immunol. (2001) [Pubmed]
  13. Cutting edge: profile of chemokine receptor expression on human plasma cells accounts for their efficient recruitment to target tissues. Nakayama, T., Hieshima, K., Izawa, D., Tatsumi, Y., Kanamaru, A., Yoshie, O. J. Immunol. (2003) [Pubmed]
  14. All-trans retinoic acid regulates CXCL16/SR-PSOX expression. Wågsäter, D., Sheikine, Y., Sirsjö, A. Int. J. Mol. Med. (2005) [Pubmed]
  15. Discovery of novel biomarkers by microarray analysis of peripheral blood mononuclear cell gene expression in benzene-exposed workers. Forrest, M.S., Lan, Q., Hubbard, A.E., Zhang, L., Vermeulen, R., Zhao, X., Li, G., Wu, Y.Y., Shen, M., Yin, S., Chanock, S.J., Rothman, N., Smith, M.T. Environ. Health Perspect. (2005) [Pubmed]
  16. CXCL16 is a novel angiogenic factor for human umbilical vein endothelial cells. Zhuge, X., Murayama, T., Arai, H., Yamauchi, R., Tanaka, M., Shimaoka, T., Yonehara, S., Kume, N., Yokode, M., Kita, T. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  17. TLR4-NOX4-AP-1 signaling mediates lipopolysaccharide-induced CXCR6 expression in human aortic smooth muscle cells. Patel, D.N., Bailey, S.R., Gresham, J.K., Schuchman, D.B., Shelhamer, J.H., Goldstein, B.J., Foxwell, B.M., Stemerman, M.B., Maranchie, J.K., Valente, A.J., Mummidi, S., Chandrasekar, B. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  18. CXC chemokine ligand 16 promotes integrin-mediated adhesion of liver-infiltrating lymphocytes to cholangiocytes and hepatocytes within the inflamed human liver. Heydtmann, M., Lalor, P.F., Eksteen, J.A., Hübscher, S.G., Briskin, M., Adams, D.H. J. Immunol. (2005) [Pubmed]
  19. The chemokine and scavenger receptor CXCL16/SR-PSOX is expressed in human vascular smooth muscle cells and is induced by interferon gamma. Wågsäter, D., Olofsson, P.S., Norgren, L., Stenberg, B., Sirsjö, A. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  20. Expression of CXCR6 and its ligand CXCL16 in the lung in health and disease. Morgan, A.J., Guillen, C., Symon, F.A., Huynh, T.T., Berry, M.A., Entwisle, J.J., Briskin, M., Pavord, I.D., Wardlaw, A.J. Clin. Exp. Allergy (2005) [Pubmed]
  21. Decreased plasma CXCL16/SR-PSOX concentration is associated with coronary artery disease. Sheikine, Y., Bang, C.S., Nilsson, L., Samnegård, A., Hamsten, A., Jonasson, L., Eriksson, P., Sirsjö, A. Atherosclerosis (2006) [Pubmed]
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