Expression and localization of CXCL16 and CXCR6 in ovarian endometriotic tissues

Purpose Inflammatory mediators, including chemokines, may play crucial roles in the development of endometriosis. Therefore, we investigated the expression and localization of CXCL16 and its receptor, CXCR6, in ovarian endometriotic tissues. We also examined whether CXCL16 induces IL-8 production in endometriotic stromal cells.

We performed immunohistochemical and Western blotting analyses of in vivo and in vitro samples. IL-8 production was assayed using an ELISA.

Both CXCL16 and CXCR6 were expressed by endometriotic epithelial cells and stromal cells, but not normal ovarian stroma. A Western blotting analysis using primary cultured endometriotic stromal cells showed a constant expression of CXCL16 and CXCR6 in the proliferative phase, secretory phase and during gonadotropin-releasing hormone agonist therapy. CXCL16 induced IL-8 production in several endometriotic stromal cells in vitro.

CXCL16 and CXCR6 might be involved in the pathophysiology of endometriosis through regulation of the inflammatory response. Similar content being viewed by others

Ozkan S, Murk W, Arici A (2008) Endometriosis and infertility: epidemiology and evidence-based treatments. Ann N Y Acad Sci 1127:92–100. doi:1127/1/92[pii]10.1196/annals.1434.007 Sampson JA (1927) Metastatic or embolic endometriosis, due to the menstrual dissemination of endometrial tissue into the venous circulation. Am J Pathol 3(2):93–110 143 de Ziegler D, Borghese B, Chapron C (2010) Endometriosis and infertility: pathophysiology and management. Lancet 376(9742):730–738. doi:S0140-6736(10)60490-4[pii]10.1016/S0140-6736(10)60490-4 Agic A, Xu H, Finas D, Banz C, Diedrich K, Hornung D (2006) Is endometriosis associated with systemic subclinical inflammation? Gynecol Obstet Invest 62(3):139–147. doi:000093121[pii]10.1159/000093121 Osuga Y (2008) Novel therapeutic strategies for endometriosis: a pathophysiological perspective. Gynecol Obstet Invest 66(Suppl 1):3–9. doi:000148025[pii]10.1159/000148025 Akoum A, Lemay A, Brunet C, Hebert J (1995) Secretion of monocyte chemotactic protein-1 by cytokine-stimulated endometrial cells of women with endometriosis Le groupe d’investigation en gynecologie. Fertil Steril 63(2):322–328 Iwabe T, Harada T, Tsudo T, Nagano Y, Yoshida S, Tanikawa M, Terakawa N (2000) Tumor necrosis factor-alpha promotes proliferation of endometriotic stromal cells by inducing interleukin-8 gene and protein expression. J Clin Endocrinol Metab 85(2):824–829 Tseng JF, Ryan IP, Milam TD, Murai JT, Schriock ED, Landers DV, Taylor RN (1996) Interleukin-6 secretion in vitro is up-regulated in ectopic and eutopic endometrial stromal cells from women with endometriosis. J Clin Endocrinol Metab 81(3):1118–1122 Luster AD (1998) Chemokines—chemotactic cytokines that mediate inflammation. N Engl J Med 338(7):436–445. doi:10.1056/NEJM199802123380706 Struyf S, Proost P, Van Damme J (2003) Regulation of the immune response by the interaction of chemokines and proteases. Adv Immunol 81:1–44 Chand AL, Murray AS, Jones RL, Hannan NJ, Salamonsen LA, Rombauts L (2007) Laser capture microdissection and cDNA array analysis of endometrium identify CCL16 and CCL21 as epithelial-derived inflammatory mediators associated with endometriosis. Reprod Biol Endocrinol 5:18. doi:1477-7827-5-18[pii]10.1186/1477-7827-5-18 Lin YJ, Lai MD, Lei HY, Wing LY (2006) Neutrophils and macrophages promote angiogenesis in the early stage of endometriosis in a mouse model. Endocrinology 147(3):1278–1286. doi:en.2005-0790[pii]10.1210/en.2005-0790 Hase K, Murakami T, Takatsu H, Shimaoka T, Iimura M, Hamura K, Kawano K, Ohshima S, Chihara R, Itoh K, Yonehara S, Ohno H (2006) The membrane-bound chemokine CXCL16 expressed on follicle-associated epithelium and M cells mediates lympho-epithelial interaction in GALT. J Immunol 176(1):43–51. doi:176/1/43[pii] Heydtmann M, Lalor PF, Eksteen JA, Hubscher SG, Briskin M, Adams DH (2005) CXC chemokine ligand 16 promotes integrin-mediated adhesion of liver-infiltrating lymphocytes to cholangiocytes and hepatocytes within the inflamed human liver. J Immunol 174(2):1055–1062. doi:174/2/1055[pii] Kim CH, Kunkel EJ, Boisvert J, Johnston B, Campbell JJ, Genovese MC, Greenberg HB, Butcher EC (2001) Bonzo/CXCR6 expression defines type 1-polarized T-cell subsets with extralymphoid tissue homing potential. J Clin Invest 107(5):595–601. doi:10.1172/JCI11902 Tabata S, Kadowaki N, Kitawaki T, Shimaoka T, Yonehara S, Yoshie O, Uchiyama T (2005) Distribution and kinetics of SR-PSOX/CXCL16 and CXCR6 expression on human dendritic cell subsets and CD4+ T cells. J Leukoc Biol 77(5):777–786. doi:jlb.1204733[pii]10.1189/jlb.1204733 Matloubian M, David A, Engel S, Ryan JE, Cyster JG (2000) A transmembrane CXC chemokine is a ligand for HIV-coreceptor Bonzo. Nat Immunol 1(4):298–304. doi:10.1038/79738 Shimaoka T, Kume N, Minami M, Hayashida K, Kataoka H, Kita T, Yonehara S (2000) Molecular cloning of a novel scavenger receptor for oxidized low density lipoprotein, SR-PSOX, on macrophages. J Biol Chem 275(52):40663–40666. doi:10.1074/jbc.C000761200C000761200[pii] Wilbanks A, Zondlo SC, Murphy K, Mak S, Soler D, Langdon P, Andrew DP, Wu L, Briskin M (2001) Expression cloning of the STRL33/BONZO/TYMSTR ligand reveals elements of CC, CXC, and CX3C chemokines. J Immunol 166(8):5145–5154 Shashkin P, Simpson D, Mishin V, Chesnutt B, Ley K (2003) Expression of CXCL16 in human T cells. Arterioscler Thromb Vasc Biol 23(1):148–149 Nanki T, Shimaoka T, Hayashida K, Taniguchi K, Yonehara S, Miyasaka N (2005) Pathogenic role of the CXCL16-CXCR6 pathway in rheumatoid arthritis. Arthritis Rheum 52(10):3004–3014. doi:10.1002/art.21301 Ruth JH, Haas CS, Park CC, Amin MA, Martinez RJ, Haines GK 3rd, Shahrara S, Campbell PL, Koch AE (2006) CXCL16-mediated cell recruitment to rheumatoid arthritis synovial tissue and murine lymph nodes is dependent upon the MAPK pathway. Arthritis Rheum 54(3):765–778. doi:10.1002/art.21662 Agostini C, Cabrelle A, Calabrese F, Bortoli M, Scquizzato E, Carraro S, Miorin M, Beghe B, Trentin L, Zambello R, Facco M, Semenzato G (2005) Role for CXCR6 and its ligand CXCL16 in the pathogenesis of T-cell alveolitis in sarcoidosis. Am J Respir Crit Care Med 172(10):1290–1298. doi:200501-142OC[pii]10.1164/rccm.200501-142OC Morgan AJ, Guillen C, Symon FA, Huynh TT, Berry MA, Entwisle JJ, Briskin M, Pavord ID, Wardlaw AJ (2005) Expression of CXCR6 and its ligand CXCL16 in the lung in health and disease. Clin Exp Allergy 35(12):1572–1580. doi:CEA2383[pii]10.1111/j.1365-2222.2005.02383.x Kita T, Kume N, Minami M, Hayashida K, Murayama T, Sano H, Moriwaki H, Kataoka H, Nishi E, Horiuchi H, Arai H, Yokode M (2001) Role of oxidized LDL in atherosclerosis. Ann N Y Acad Sci 947:199–205 discussion 205–196 Sheikine Y, Hansson GK (2004) Chemokines and atherosclerosis. Ann Med 36(2):98–118 Wuttge DM, Zhou X, Sheikine Y, Wagsater D, Stemme V, Hedin U, Stemme S, Hansson GK, Sirsjo A (2004) CXCL16/SR-PSOX is an interferon-gamma-regulated chemokine and scavenger receptor expressed in atherosclerotic lesions. Arterioscler Thromb Vasc Biol 24(4):750–755. doi:10.1161/01.ATV.0000124102.11472.3601.ATV.0000124102.11472.36[pii] Iwase A, Ando H, Nagasaka T, Goto M, Harata T, Kikkawa F (2007) Distribution of endothelin-converting enzyme-1 and neutral endopeptidase in human endometrium. J Histochem Cytochem 55(12):1229–1235. doi:jhc.7A7274.2007[pii]10.1369/jhc.7A7274.2007 Iwase A, Ando H, Nagasaka T, Shibata D, Harata T, Shimomura Y, Goto M, Kikkawa F (2006) Neutral endopeptidase expressed by decidualized stromal cells suppresses akt phosphorylation and deoxyribonucleic acid synthesis induced by endothelin-1 in human endometrium. Endocrinology 147(11):5153–5159. doi:en.2006-0172[pii]10.1210/en.2006-0172 Kim CH, Johnston B, Butcher EC (2002) Trafficking machinery of NKT cells: shared and differential chemokine receptor expression among V alpha 24(+)V beta 11(+) NKT cell subsets with distinct cytokine-producing capacity. Blood 100(1):11–16. doi:10.1182/blood-2001-12-0196 Unutmaz D, Xiang W, Sunshine MJ, Campbell J, Butcher E, Littman DR (2000) The primate lentiviral receptor Bonzo/STRL33 is coordinately regulated with CCR5 and its expression pattern is conserved between human and mouse. J Immunol 165(6):3284–3292. doi:ji_v165n6p3284[pii] Volin MV, Woods JM, Amin MA, Connors MA, Harlow LA, Koch AE (2001) Fractalkine: a novel angiogenic chemokine in rheumatoid arthritis. Am J Pathol 159(4):1521–1530. doi:S0002-9440(10)62537-0[pii]10.1016/S0002-9440(10)62537-0 Hanamoto H, Nakayama T, Miyazato H, Takegawa S, Hieshima K, Tatsumi Y, Kanamaru A, Yoshie O (2004) Expression of CCL28 by Reed-Sternberg cells defines a major subtype of classical Hodgkin’s disease with frequent infiltration of eosinophils and/or plasma cells. Am J Pathol 164(3):997–1006. doi:S0002-9440(10)63187-2[pii]10.1016/S0002-9440(10)63187-2 Wagsater D, Dimberg J (2004) Expression of chemokine receptor CXCR6 in human colorectal adenocarcinomas. Anticancer Res 24(6):3711–3714 Darash-Yahana M, Gillespie JW, Hewitt SM, Chen YY, Maeda S, Stein I, Singh SP, Bedolla RB, Peled A, Troyer DA, Pikarsky E, Karin M, Farber JM (2009) The chemokine CXCL16 and its receptor, CXCR6, as markers and promoters of inflammation-associated cancers. PLoS One 4(8):e6695 10.1371/journal.pone.0006695 Shimaoka T, Nakayama T, Fukumoto N, Kume N, Takahashi S, Yamaguchi J, Minami M, Hayashida K, Kita T, Ohsumi J, Yoshie O, Yonehara S (2004) Cell surface-anchored SR-PSOX/CXC chemokine ligand 16 mediates firm adhesion of CXC chemokine receptor 6-expressing cells. J Leukoc Biol 75(2):267–274. doi:10.1189/jlb.1003465jlb.1003465[pii] Abel S, Hundhausen C, Mentlein R, Schulte A, Berkhout TA, Broadway N, Hartmann D, Sedlacek R, Dietrich S, Muetze B, Schuster B, Kallen KJ, Saftig P, Rose-John S, Ludwig A (2004) 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. J Immunol 172(10):6362–6372 Gough PJ, Garton KJ, Wille PT, Rychlewski M, Dempsey PJ, Raines EW (2004) A disintegrin and metalloproteinase 10-mediated cleavage and shedding regulates the cell surface expression of CXC chemokine ligand 16. J Immunol 172(6):3678–3685 Finas D, Huszar M, Agic A, Dogan S, Kiefel H, Riedle S, Gast D, Marcovich R, Noack F, Altevogt P, Fogel M, Hornung D (2008) L1 cell adhesion molecule (L1CAM) as a pathogenetic factor in endometriosis. Hum Reprod 23(5):1053–1062. doi:den044[pii]10.1093/humrep/den044 Baston-Bust DM, Gotte M, Janni W, Krussel JS, Hess AP (2010) Syndecan-1 knock-down in decidualized human endometrial stromal cells leads to significant changes in cytokine and angiogenic factor expression patterns. Reprod Biol Endocrinol 8:133. doi:1477-7827-8-133[pii]10.1186/1477-7827-8-133 Koch AE, Polverini PJ, Kunkel SL, Harlow LA, DiPietro LA, Elner VM, Elner SG, Strieter RM (1992) Interleukin-8 as a macrophage-derived mediator of angiogenesis. Science 258(5089):1798–1801 Arici A, Seli E, Zeyneloglu HB, Senturk LM, Oral E, Olive DL (1998) Interleukin-8 induces proliferation of endometrial stromal cells: a potential autocrine growth factor. J Clin Endocrinol Metab 83(4):1201–1205 Conflict of interest None. Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Manabe, S., Iwase, A., Goto, M. et al. Expression and localization of CXCL16 and CXCR6 in ovarian endometriotic tissues. Arch Gynecol Obstet 284, 1567–1572 (2011). https://doi.org/10.1007/s00404-011-2002-y Received: Accepted: Published: Issue date: DOI: https://doi.org/10.1007/s00404-011-2002-y