Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human immunodeficiency virus-1 (HIV-1)-Tat, the transactivating gene product of HIV-1, has been shown to interact with different cell types, inducing gene expression, altering their growth and migratory behavior. In this study we examined whether Tat might affect functions of acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin's lymphoma (NHL), relevant to the in vivo dissemination. Our results show that Tat significantly augmented the motility of the two AIDS-related Burkitt's lymphoma cell lines (AS283 and PA682PB) and AIDS-primary effusion lymphoma cell line (HBL-6-AIDS-PEL). Mutations in RGD or basic domain of Tat (KGE-MBP and LxI-MBP, respectively) sharply reduced migration compared with wild type, suggesting that both domains are required for migration. In contrast, a Tat protein mutation outside the active domains (NH(2)-TAT-GST) did not reduce lymphoma cell migration. The treatment of lymphoma cells with Tat did not influence their adhesion to matrix proteins or to human vascular endothelial cells, but endothelial cells treated with Tat became more adhesive to lymphoma cells. Flow cytometric analysis showed that treatment of endothelial cells with Tat induced the cell surface expression of the adhesion molecules vascular cell adhesion molecule-1 (VCAM-1) and E-selectin and increased the expression of intercellular adhesion molecule-1 (ICAM-1). Only antibodies against VCAM-1 on endothelial cells or against the VLA-4 integrin expressed on AS283 cells inhibited the increment of adhesion, indicating the relevance of this pathway in the adhesion of lymphoma cells to vascular endothelium. In our work, we show for the first time that Tat can enhance the migration of lymphoma cells and their adhesion to endothelial cells, two processes that may contribute to the malignant behavior of NHL in patients with AIDS.
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PMID:Human immunodeficiency virus-1 (HIV-1)-Tat protein promotes migration of acquired immunodeficiency syndrome-related lymphoma cells and enhances their adhesion to endothelial cells. 1047

Lymphoid organ development and inflammation have previously been considered as distinct mechanistically and functionally. In recent years, it has been realized that these phenomena have much in common. This insight has been gained from the recognition that cytokines of the lymphotoxin (LT)/tumor necrosis factor (TNF) family are involved in both processes. The members of the family, LT-alpha, LT-beta, and TNF-alpha, and their multiple receptors participate combinatorially in lymphoid organ development and chronic inflammation. When inflammation that arises in microbial infection or autoimmune disease becomes chronic, it can take on the appearance of organized lymphoid tissue and has been called a tertiary lymphoid organ. Data with transgenic and knockout mice suggest that the process is cytokine-mediated and could be called "lymphoid neo-organogenesis." LT as LT-alpha3 and LT-alpha1beta2 plays a key role in these processes. Data obtained in vitro in an endothelial cell line and in vivo in transgenic and knockout mice indicate that LT influences these events through induction of adhesion molecules such as E-selectin adhesion molecule (ELAM), vascular cell adhesion molecule (VCAM), intercellular adhesion molecule (ICAM), mucosal addressin cellular adhesion molecule (MAdCAM), and peripheral node addressin (PNAd), and chemokines.
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PMID:Lymphoid neo-organogenesis: lymphotoxin's role in inflammation and development. 1049 67