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Gene Review

CCL18  -  chemokine (C-C motif) ligand 18 (pulmonary...

Homo sapiens

Synonyms: AMAC-1, AMAC1, Alternative macrophage activation-associated CC chemokine 1, C-C motif chemokine 18, CC chemokine PARC, ...
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Disease relevance of CCL18


High impact information on CCL18

  • We show that DC-CK1, in contrast to RANTES, MIP-1alpha and interleukin-8, preferentially attracts naive T cells (CD45RA+) [6].
  • Here we report the identification and characterization of a C-C chemokine (DC-CK1) that is specifically expressed by human dendritic cells at high levels [6].
  • The specific expression of DC-CK1 by dendritic cells at the site of initiation of an immune response, combined with its chemotactic activity for naive T cells, suggests that DC-CK1 has an important rule in the induction of immune responses [6].
  • METHODS: We identified a specific gene of interest, chemokine (C-C motif) ligand 18 (CCL18), on the basis of a high absolute standardized log Cox hazard ratio, a high variance in expression among all tumor samples, and putative biologic function [7].
  • We found that CCL18 was expressed by a subpopulation of tumor-associated macrophages that were preferentially located at the tumor invasion front [7].

Chemical compound and disease context of CCL18

  • In vivo, topical exposure to the relevant allergen or the superantigen staphylococcal enterotoxin B, resulted in a significant induction of CCL18 in atopic dermatitis patients [8].

Biological context of CCL18


Anatomical context of CCL18

  • Therefore, CCL18 may act as a chemotactic signal that promotes the colocalization of immature DC with naive T lymphocytes in an IL-10-dominated environment with the consequent generation of T regulatory cells [12].
  • Unique regulation of CCL18 production by maturing dendritic cells [12].
  • In ascitic fluids from patients with ovarian carcinoma (n = 12), significantly higher levels of CXCL8 and CCL18 (2.0 versus 0.7 ng/ml (p = 0.01) and 120 versus 44 ng/ml (p = 0.0002), respectively) were detected compared with those in nonovarian carcinoma patients (n = 12) [2].
  • In contrast to CXCL8, CCL18 was not inducible in carcinoma cell lines [2].
  • Binding analysis using PARC fused with alkaline phosphatase-(His)6 showed the presence of a single class of receptors for PARC on lymphocytes with a Kd of 1.9 nM and 590 sites/cell [13].

Associations of CCL18 with chemical compounds

  • In contrast, FcgammaR stimulation inhibited the IL-10- and LPS-mediated induction of CCL18 [14].
  • Furthermore, in nonatopic NiSO4-sensitized individuals, only relevant allergen but not irritant exposure resulted in the induction of CCL18 [8].
  • Functionally, CCL18 preferentially attracted in vitro-polarized Th2 cells and basophils, but not eosinophils and Th1 cells, and induced basophil histamine and intracellular calcium release [15].
  • Out of the three immunomodulatory drugs tested, Dx downregulates PARC mRNA expression in BALF cells in vitro [16].
  • A combination of total protein, glucose, IL-8, PARC and IP-10 CSF levels proved to be most discriminative between LM and non-LM patients [17].

Regulatory relationships of CCL18


Other interactions of CCL18

  • MIP4 may therefore use chemokine receptor agonism and antagonism to control leukocyte movement in vivo [19].
  • Surprisingly, the unmodified MIP4 protein, which is known to act as a T cell chemoattractant, also exhibits this CCR3 antagonistic activity, although to a lesser extent than Met-Ckbeta7, but to a level that may be of physiological relevance [19].
  • IL-10 and vitamin D(3), two known inhibitors of DC differentiation and function, strongly promoted CCL18 secretion, whereas IFN-gamma, a costimulator of DC function, inhibited its production [12].
  • In synovial fluids from septic and rheumatoid arthritis patients, fourfold-enhanced CCL18/PARC levels (150 ng/ml) were detected compared to those in crystal-induced arthritis and osteoarthritis [4].
  • In temporal arteries affected by giant cell arteritis, DCs are highly enriched and activated and have matured into fully differentiated cells producing the chemokines, CCL18, CCL19, and CCL21 [20].

Analytical, diagnostic and therapeutic context of CCL18


  1. Genetic variation in the CCL18-CCL3-CCL4 chemokine gene cluster influences HIV Type 1 transmission and AIDS disease progression. Modi, W.S., Lautenberger, J., An, P., Scott, K., Goedert, J.J., Kirk, G.D., Buchbinder, S., Phair, J., Donfield, S., O'Brien, S.J., Winkler, C. Am. J. Hum. Genet. (2006) [Pubmed]
  2. Identification of biologically active chemokine isoforms from ascitic fluid and elevated levels of CCL18/pulmonary and activation-regulated chemokine in ovarian carcinoma. Schutyser, E., Struyf, S., Proost, P., Opdenakker, G., Laureys, G., Verhasselt, B., Peperstraete, L., Van de Putte, I., Saccani, A., Allavena, P., Mantovani, A., Van Damme, J. J. Biol. Chem. (2002) [Pubmed]
  3. PARC/CCL18 is a plasma CC chemokine with increased levels in childhood acute lymphoblastic leukemia. Struyf, S., Schutyser, E., Gouwy, M., Gijsbers, K., Proost, P., Benoit, Y., Opdenakker, G., Van Damme, J., Laureys, G. Am. J. Pathol. (2003) [Pubmed]
  4. Selective induction of CCL18/PARC by staphylococcal enterotoxins in mononuclear cells and enhanced levels in septic and rheumatoid arthritis. Schutyser, E., Struyf, S., Wuyts, A., Put, W., Geboes, K., Grillet, B., Opdenakker, G., Van Damme, J. Eur. J. Immunol. (2001) [Pubmed]
  5. CCL18 as an indicator of pulmonary fibrotic activity in idiopathic interstitial pneumonias and systemic sclerosis. Prasse, A., Pechkovsky, D.V., Toews, G.B., Schäfer, M., Eggeling, S., Ludwig, C., Germann, M., Kollert, F., Zissel, G., Müller-Quernheim, J. Arthritis Rheum. (2007) [Pubmed]
  6. A dendritic-cell-derived C-C chemokine that preferentially attracts naive T cells. Adema, G.J., Hartgers, F., Verstraten, R., de Vries, E., Marland, G., Menon, S., Foster, J., Xu, Y., Nooyen, P., McClanahan, T., Bacon, K.B., Figdor, C.G. Nature (1997) [Pubmed]
  7. Expression profiling identifies chemokine (C-C motif) ligand 18 as an independent prognostic indicator in gastric cancer. Leung, S.Y., Yuen, S.T., Chu, K.M., Mathy, J.A., Li, R., Chan, A.S., Law, S., Wong, J., Chen, X., So, S. Gastroenterology (2004) [Pubmed]
  8. CC chemokine ligand 18, an atopic dermatitis-associated and dendritic cell-derived chemokine, is regulated by staphylococcal products and allergen exposure. Pivarcsi, A., Gombert, M., Dieu-Nosjean, M.C., Lauerma, A., Kubitza, R., Meller, S., Rieker, J., Muller, A., Da Cunha, L., Haahtela, A., Sonkoly, E., Fridman, W.H., Alenius, H., Kemeny, L., Ruzicka, T., Zlotnik, A., Homey, B. J. Immunol. (2004) [Pubmed]
  9. Chemokine PARC gene (SCYA18) generated by fusion of two MIP-1alpha/LD78alpha-like genes. Tasaki, Y., Fukuda, S., Iio, M., Miura, R., Imai, T., Sugano, S., Yoshie, O., Hughes, A.L., Nomiyama, H. Genomics (1999) [Pubmed]
  10. CCL18/PARC stimulates hematopoiesis in long-term bone marrow cultures indirectly through its effect on monocytes. Wimmer, A., Khaldoyanidi, S.K., Judex, M., Serobyan, N., Discipio, R.G., Schraufstatter, I.U. Blood (2006) [Pubmed]
  11. Distinct gene expression profiles in different B-cell compartments in human peripheral lymphoid organs. Shen, Y., Iqbal, J., Xiao, L., Lynch, R.C., Rosenwald, A., Staudt, L.M., Sherman, S., Dybkaer, K., Zhou, G., Eudy, J.D., Delabie, J., McKeithan, T.W., Chan, W.C. BMC Immunol. (2004) [Pubmed]
  12. Unique regulation of CCL18 production by maturing dendritic cells. Vulcano, M., Struyf, S., Scapini, P., Cassatella, M., Bernasconi, S., Bonecchi, R., Calleri, A., Penna, G., Adorini, L., Luini, W., Mantovani, A., Van Damme, J., Sozzani, S. J. Immunol. (2003) [Pubmed]
  13. A novel human CC chemokine PARC that is most homologous to macrophage-inflammatory protein-1 alpha/LD78 alpha and chemotactic for T lymphocytes, but not for monocytes. Hieshima, K., Imai, T., Baba, M., Shoudai, K., Ishizuka, K., Nakagawa, T., Tsuruta, J., Takeya, M., Sakaki, Y., Takatsuki, K., Miura, R., Opdenakker, G., Van Damme, J., Yoshie, O., Nomiyama, H. J. Immunol. (1997) [Pubmed]
  14. Differential regulation of chemokine production by Fcgamma receptor engagement in human monocytes: association of CCL1 with a distinct form of M2 monocyte activation (M2b, Type 2). Sironi, M., Martinez, F.O., D'Ambrosio, D., Gattorno, M., Polentarutti, N., Locati, M., Gregorio, A., Iellem, A., Cassatella, M.A., Van Damme, J., Sozzani, S., Martini, A., Sinigaglia, F., Vecchi, A., Mantovani, A. J. Leukoc. Biol. (2006) [Pubmed]
  15. Involvement of CCL18 in Allergic Asthma. Nadaï, P., Charbonnier, A.S., Chenivesse, C., Sénéchal, S., Fournier, C., Gilet, J., Vorng, H., Chang, Y., Gosset, P., Wallaert, B., Tonnel, A.B., Lassalle, P., Tsicopoulos, A. J. Immunol. (2006) [Pubmed]
  16. Expression of the chemokine PARC mRNA in bronchoalveolar cells of patients with sarcoidosis. Mrazek, F., Sekerova, V., Drabek, J., Kolek, V., du Bois, R.M., Petrek, M. Immunol. Lett. (2002) [Pubmed]
  17. CSF protein profiling using Multiplex Immuno-assay : A potential new diagnostic tool for leptomeningeal metastases. Brandsma, D., Voest, E.E., de Jager, W., Bonfrer, H., Algra, A., Boogerd, W., Korse, T., Reijneveld, J.C., Verbeek, M.M., Rijkers, G., Taphoorn, M.J. J. Neurol. (2006) [Pubmed]
  18. Alternative macrophage activation-associated CC-chemokine-1, a novel structural homologue of macrophage inflammatory protein-1 alpha with a Th2-associated expression pattern. Kodelja, V., Müller, C., Politz, O., Hakij, N., Orfanos, C.E., Goerdt, S. J. Immunol. (1998) [Pubmed]
  19. C-C chemokine receptor 3 antagonism by the beta-chemokine macrophage inflammatory protein 4, a property strongly enhanced by an amino-terminal alanine-methionine swap. Nibbs, R.J., Salcedo, T.W., Campbell, J.D., Yao, X.T., Li, Y., Nardelli, B., Olsen, H.S., Morris, T.S., Proudfoot, A.E., Patel, V.P., Graham, G.J. J. Immunol. (2000) [Pubmed]
  20. Trapping of misdirected dendritic cells in the granulomatous lesions of giant cell arteritis. Krupa, W.M., Dewan, M., Jeon, M.S., Kurtin, P.J., Younge, B.R., Goronzy, J.J., Weyand, C.M. Am. J. Pathol. (2002) [Pubmed]
  21. Induction of prolonged infiltration of T lymphocytes and transient T lymphocyte-dependent collagen deposition in mouse lungs following adenoviral gene transfer of CCL18. Luzina, I.G., Papadimitriou, J.C., Anderson, R., Pochetuhen, K., Atamas, S.P. Arthritis Rheum. (2006) [Pubmed]
  22. A Vicious Circle of Alveolar Macrophages and Fibroblasts Perpetuates Pulmonary Fibrosis via CCL18. Prasse, A., Pechkovsky, D.V., Toews, G.B., Jungraithmayr, W., Kollert, F., Goldmann, T., Vollmer, E., Müller-Quernheim, J., Zissel, G. Am. J. Respir. Crit. Care Med. (2006) [Pubmed]
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