Upregulation of CC chemokine ligand 18 and downregulation of CX3C chemokine receptor 1 expression in human T-cell leukemia virus type 1-associated lymph node lesions: Results of chemokine and chemokine receptor DNA chip analysis.
Adult T-cell leukemia/lymphoma (ATLL) is a human malignancy associated with human T-cell leukemia virus type 1 (HTLV-1). The pathological features of the lymph nodes of ATLL change from those of lymphadenitis to Hodgkin's-like features and those of lymphoma. Chemokines and their receptors are closely associated with T-cell subgroups and immune responses. To clarify the relationship between chemokines and their receptor expression, as well as the development of ATLL, 17 cases with ATLL were analyzed using DNA chips of chemokines and their receptors. All cases showed a varied and mixed pattern of upregulated and downregulated gene expression of Th1, Th2, naïve, and cytotoxic cell-associated chemokine genes. As CC chemokine ligand 18 (CCL18) accounted for the most upregulated gene and CX3C chemokine receptor 1 (CX3CR1) for the most downregulated gene, they were selected for immunohistochemical analysis. Immunohistochemical staining showed expression of the two genes in immunological cells, with a positive expression for reticulum cells, but not for ATLL cells. HTLV-1-associated lymphadenitis type (n = 13) and Hodgkin's-like type (n = 12) cases showed significantly higher CCL18 expression than the non-specific lymphadenitis cases (n = 10) (P < 0.05). However, all HTLV-1-associated cases showed significantly lower CX3CR1 expression than the non-specific lymphadenitis cases (P < 0.05). These results suggest that upregulation of CCL18 expression and downregulation of CX3CR1 expression play a role in immune responses against the ATLL cells.
Shimizu
Kei
K
Department of Pathology, School of Medicine, Kurume University, 67 Asahi-machi, Kurume, Fukuoka, Japan.
Karube
Kennosuke
K
Arakawa
Fumiko
F
Nomura
Yuko
Y
Komatani
Hideki
H
Yamamoto
Kouhei
K
Yoshida
Shiro
S
Aoki
Ryosuke
R
Sugita
Yasuo
Y
Takeshita
Morishige
M
Ohshima
Koichi
K
D000073883:CX3C Chemokine Receptor 1; D019742:Chemokines, CC / Q000235:genetics*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D015490:HTLV-I Infections / Q000473:pathology / Q000503:physiopathology*; D015368:Human T-lymphotropic virus 1 / Q000472:pathogenicity*; D006801:Humans; D007150:Immunohistochemistry; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D008198:Lymph Nodes / Q000473:pathology* / Q000821:virology; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D019707:Receptors, Chemokine / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
C111792:CCL18 protein, human; D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D019742:Chemokines, CC; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D019707:Receptors, Chemokine