title: Expression of chemokine and receptors in Lewis rats with experimental autoimmune anterior uveitis.
abstract: The purpose of this study is to investigate the sequential expression of certain chemokines and chemokine receptors in the iris-ciliary body and popliteal lymph nodes of Lewis rats and, thus, to establish their roles in experimental autoimmune anterior uveitis. Uveitis was induced with the injection of melanin-associated antigen intraperitoneally and into the left foot. The clinical severity of the uveitis was scored. At defined time points, CC chemokines (monocyte chemoattractant protein-1, macrophage inflammatory protein-1, and regulated-upon-activation normal T-cell expressed and secreted), CXC chemokines (interferon gamma-inducible protein-10, stromal-derived factor-1, and interleukin-8), and receptor (CCR2, CCR3, CCR5, CXCR1, CXCR2, CXCR3, and CXCR4) mRNA expression were semiquantified by using a reverse-transcriptase reaction followed by polymerase chain reaction. The concentrations of macrophage inflammatory protein-1 and regulated-upon-activation normal T-cell expressed and secreted in aqueous humor were determined by means of enzyme-linked immunosorbent assay. Levels of monocyte chemoattractant protein-1, macrophage inflammatory protein-1 and interferon gamma-inducible protein-10 started increasing before the clinical onset of disease; these might have been involved in the initial recruitment of inflammatory cells. The level of regulated-upon-activation normal T-cell mRNA, however, started rising concurrently with the onset of clinical disease, suggesting that this chemokine may exert amplifying role in generating uveitis. Stromal-derived factor-1 exhibited an early and high level of expression with the increase of cognate receptor, CXCR4, indicating that stromal-derived factor-1 plays a role in either promoting angiogenesis or attracting for T-cells. Instead of upregulation like other chemokine receptors, interleukin-8 receptors, CXCR1and CXCR2, mRNA could not be detected in accord with the increase of interleukin-8. These findings appeared that downregulation of chemokine receptors on neutrophils may make themselves less respond to interleukin-8 and subsequently lead to decreased recruitment of neutrophils into the iris-ciliary body. In addition, the expression of chemokine receptors in popliteal lymph nodes were earlier than those in the iris-ciliary body. This sequence of expression may reflect the process of T lymphocytes maturation and differentiation. Monocyte chemoattractant protein-1 protein was immunohistologically detected in the ciliary epithelium and infiltrating leukocytes. The above results suggest that chemokines, which act on T cells and monocytes, are sequentially upregulated during the clinical course of experimental autoimmune anterior uveitis, and thus, may contribute to the pathogenesis of acute anterior uveitis.
authors.affiliation: Department of Ophthalmology, National Taiwan University Hospital, No. 7, Section 1, Chung-Shan South Road, Taipei 100, Taiwan, ROC.
authors.forename: I-Mo
authors.initials: IM
authors.lastname: Fang
authors.forename: Chang-Hao
authors.initials: CH
authors.lastname: Yang
authors.forename: Chang-Pin
authors.initials: CP
authors.lastname: Lin
authors.forename: Chung-May
authors.initials: CM
authors.lastname: Yang
authors.forename: Muh-Shy
authors.initials: MS
authors.lastname: Chen
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D018932:Chemokine CCL2 / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D002924:Ciliary Body / Q000276:immunology; D015870:Gene Expression; D007498:Iris / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000276:immunology; D014606:Uveitis, Anterior / Q000276:immunology*
chemical_list: D018932:Chemokine CCL2; D018946:Chemokine CCL5; D018925:Chemokines; D012333:RNA, Messenger; D019707:Receptors, Chemokine