Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experiments were carried out to study the mechanism of the induction of ornithine decarboxylase (ODC) in mouse tissues by the injection of a lipopolysaccharide (LPS). In addition to LPS, various mitogenic substances, such as concanavalin A, pokeweed mitogen, polyI:polyC and a phorbol diester, induced ODC in the liver and the spleen of mice at 4.5 hr after injection. Non-mitogenic immuno-stimulants or inflammatory agents, such as zymosan, carrageenan, N-acetylmuramyl-L-alanyl-D-isoglutamine, glycogen, D-galactosamine and interferon, did not induce the enzyme. ODC induction by LPS in C3H/HeJ mice, the lymphocytes and/or macrophages of which are known to be less responsive to LPS, was much less than in C3H/He and ddI mice. ODC induction by LPS was suppressed by dexamethasone and cycloheximide. Actinomycin D did not suppress ODC induction by LPS but, rather, enhanced it. These results suggest that (1) lymphocytes and/or macrophages may participate in the induction of ODC by mitogenic substances as well as by LPS, (2) ODC may be induced by mitogenic substances without the synthesis of RNA, and (3) the translation of existing RNA may be accelerated by actinomycin D.
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PMID:Induction of ornithine decarboxylase in mouse tissues following the injection of mitogenic substances. Enhancement by actinomycin D. 674 56

2',3'-Dideoxyinosine (ddI) is a purine nucleoside analog currently being used for the treatment of HIV-positive individuals and patients with AIDS. Preliminary immunotoxicity studies have shown that a consequence of ddI treatment in female B6C3F1 mice is the inhibition of the humoral immune response. This effect was dose dependent in a range of 100 to 1000 mg/kg with a no observed adverse effect level of less than 100 mg/kg for a 28-day treatment period. These studies were undertaken to investigate the immune cell target of ddI and to determine the mechanism of this toxicity. B6C3F1 mice were treated with 1000 mg/kg/day by oral gavage for 28 days. The B lymphocyte was identified as the cellular target of ddI through separation-reconstitution experiments of the adherent and nonadherent cell populations and of the T and B lymphocyte populations. These studies revealed a deficit in the ability of the nonadherent cells from ddI-treated mice to mount a normal antibody response to sRBC. A further separation of the nonadherent cells into T and B cells revealed a decreased ability of ddI-treated B cells to develop specific humoral immunity. Additional studies were undertaken to determine the mechanism by which ddI is affecting the B cell. Surface marker analysis of splenocytes revealed no difference in the cell populations between vehicle- and ddI-treated mice. B cell proliferation was also unaffected as shown by incubation with either a polyclonal stimulator, lipopolysaccharide, or anti-IgM plus IL-4. These results indicate that the primary cellular target of ddI is the B lymphocyte.
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PMID:2'3'-Dideoxyinosine inhibits the humoral immune response in female B6C3F1 mice by targeting the B lymphocyte. 926 98