interleukin-8 and Lymphoma--AIDS-Related

The pathogenesis of acquired immunodeficiency syndrome-associated primary central nervous system lymphoma (AIDS-associated PCNSL) remains unclear. However, cell adhesion molecules have been reported to be strongly associated with PCNSL. In this study, we established Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCLs) from HIV-positive patients (LCL(HIV)) and normal individuals (LCL(N)). The expression of CD18 antigen by LCL(HIV) was stronger than that by LCL(N). We performed a cell adhesion assay using ISO-HAS, which is the human hemangiosarcoma cell line and expresses intercellular adhesion molecule 1 (CD54). The binding rates of LCL(HIV) and ISO-HAS without stimulation were higher than those of LCL(N). Further, we demonstrated that azidothymidine or simvastatin inhibited the binding rates of LCL(HIV) and ISO-HAS more significantly than those of LCL(N). Further, the levels of interleukin (IL)-8, a CD18 inducer, were higher in LCL(HIV) than in LCL(N). We conclude that interaction between IL-8 and CD18 may be critical to AIDS-related PCNSL.

Topics: Anti-HIV Agents; CD18 Antigens; Cell Adhesion; Cell Line, Transformed; Cell Line, Tumor; Central Nervous System Neoplasms; Herpesvirus 4, Human; HIV; Humans; Intercellular Adhesion Molecule-1; Interleukin-8; Lymphoma, AIDS-Related; Simvastatin; Zidovudine

Interleukin 8 (IL-8), a member of the CXC subfamily of chemokines, is a potent inflammatory cytokine produced by many cell types in response to several stimuli. In an attempt to determine whether human B-cell IL-8 functions as an autocrine growth factor, a wide panel of B-cell lines derived from patients with AIDS-associated B-cell lymphomas (AABCL) (n = 5) and from non-AABCLs (n = 8) was studied for expression of IL-8, IL-8 Receptor type A (IL-8R), and secretion of IL-8 protein. Using RT-PCR and Northern Blot analysis, we were able to observe IL-8 expression ubiquitously. However, IL-8R expression was seen only in EBV negative (4 out of 7) B-cell lines. EBV and HIV-1 activated B-cell line; HBL-1, was the major secretor of IL-8. Our results demonstrate that IL-8 is expressed in malignant B-cell phenotypes that correspond to a narrow window in the B-cell differentiation pathway (pre-B, early-B, and intermediate-B) as well as in normal CD19-enriched B-cells. Furthermore, IL-8 autocrine loops were not evident since IL-8R was detected only in cell lines that did not secrete IL-8 protein.

Topics: B-Lymphocytes; Base Sequence; Blotting, Northern; Burkitt Lymphoma; Cloning, Molecular; DNA Primers; Glyceraldehyde-3-Phosphate Dehydrogenases; Humans; Interleukin-8; Lymphoma, AIDS-Related; Lymphoma, B-Cell; Receptors, Interleukin-8A; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Neoplasm; Tumor Cells, Cultured

In order to gain further understanding of the role of chemokines in healthy oral mucosa, we analyzed mRNA expression of the alpha (CXC)-family chemokines IL-8 and GROgamma as well as of the beta (CC)-family chemokines MIP-1alpha, MIP-1beta and MCP-1 in twenty young and healthy subjects with good oral hygiene. Twenty biopsies were taken from clinically healthy oral mucosa before surgical removal of impacted wisdom teeth. In addition, five biopsies from patients presenting with specific oral lesions were studied. RNA was purified, quantitated and utilized as substrate for competitive reverse transcription-polymerase chain reaction (RT-PCR). In healthy tissue, IL-8 and MCP-1 mRNA was constitutively expressed in all biopsies, whereas GROgamma, MIP-1alpha, and MIP-1beta were significantly lower. These findings suggest that IL8 and MCP-1 play a significant role in oral tissue homeostasis. The few samples from pathological conditions encourage exploring diseased tissue in more detail.

Topics: Adolescent; Adult; Analysis of Variance; Biopsy; Chemokine CCL2; Chemokine CCL3; Chemokine CCL4; Chemokine CXCL1; Chemokines, CC; Chemokines, CXC; Chemotactic Factors; Female; Fibroma; Gene Expression Regulation; Gingival Neoplasms; Growth Inhibitors; Growth Substances; Hemostasis; Humans; Intercellular Signaling Peptides and Proteins; Interleukin-8; Lichen Planus, Oral; Lymphoma, AIDS-Related; Macrophage Inflammatory Proteins; Male; Mouth Diseases; Mouth Mucosa; Mouth Neoplasms; Polymerase Chain Reaction; RNA, Messenger