Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the effect of levamisole (LMS) on the proliferative response and interleukin-2 (IL-2) concentration in OKT3-, phytohemagglutinin-, and concanavalin-A-stimulated lymphocyte cultures. Although proliferative response was enhanced in lymphocyte cultures stimulated in the presence of LMS, similar levels of IL-2 were observed in stimulated and unstimulated cultures. The mechanism of the enhancement effect of LMS on proliferative response was further characterized by studying its effects on the growth of IL-2-dependent CTLL-2 cells in culture. Since this cell line has been shown to require 2-mercaptoethanol (2-ME) for normal growth in recombinant IL-2, the effect of LMS on several parameters of its growth was compared with that of 2-ME. Unlike 2-ME, LMS did not enhance 35S-cystine uptake. Both compounds increased thiol concentration in the cell culture, but (oxidized) 2-ME induced a greater increase. Generally, the effects of LMS on CTLL-2 growth were quite similar to those of structurally unrelated compounds known to have antioxidant properties, and the demonstrated thiol requirement of this cell line for growth in recombinant IL-2 was met by substituting LMS for 2-ME. When the effect of LMS on IL-2 receptor (IL-2R) expression in CTLL-2 cells was examined by a receptor-ligand binding assay involving low levels (10-80 pM) of 125IL-2, a modest increase in the level of IL-2R expression was observed. The biologically active high-affinity IL-2R complex is believed to be preferentially bound at the low levels of 125IL-2 used here, suggesting a functional relevance for this effect of LMS. These observations should be useful in minimizing the cost and duration of in vitro expansion of lymphocytes for use in adoptive immunotherapy and should be applicable in improving the response of immunologically impaired patients to immunotherapy.
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PMID:Levamisole meets sulfhydryl requirements of CTLL-2 cells and mediates enhanced proliferative response to mitogen stimulation without increasing interleukin-2 production. 238 Jul 43

The mouse cytotoxic T cell clone (CTLL-2) was able to grow in the presence of culture medium supplemented only with transferrin, 2-mercaptoethanol, and recombinant interleukin 2 (IL-2). This lymphokine stimulated the synthesis of DNA in these cells. Similarly, phorbol esters, which activate protein kinase C, induced DNA synthesis in this clone. Furthermore, this later proliferation was not blocked by anti-IL-2 receptor antibodies, which inhibited IL-2-induced proliferation, suggesting that it was not indirectly due to the secretion of IL-2 by the cells. CTLL-2 cells pretreated with high doses of phorbol esters for 48 h down regulated protein kinase C and were depleted of this enzyme. This was shown by: 1) purification and in vitro assay of protein kinase C; 2) the lack of effect of phorbol esters in the stimulation of the Na+/H+ anti-porter which has been directly linked to the activation of protein kinase C. As expected, those protein kinase C-depleted cells no longer synthesized DNA and proliferated in response to phorbol esters. However, they proliferated identically to control cells in response to IL-2. Therefore, our results suggest two different pathways for T cell proliferation, one which involves protein kinase C and the other which does not.
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PMID:The role of protein kinase C in T lymphocyte proliferation. Existence of protein kinase C-dependent and -independent pathways. 284 66

The use of normobaric exposure to O2 as a model for in vitro oxidative injury prevented phytohaemagglutinin (PHA)-stimulated human peripheral blood mononuclear cells (PBMC) from undergoing the G0 to G1 transition, but 5 x 10(-6) M 2-mercaptoethanol (2-ME) almost protected the cells from this blockade. The percentage of cells with IL-2 and transferrin-receptors was reduced by the O2 exposure and, like the cell cycle transition, was protected by 2-ME against oxidative injury. By contrast, IL-2 recovery in the supernatants of O2-exposed PHA-stimulated PBMC was enhanced. This enhancement may be due partly to the reduced IL-2 consumption caused by the decreases in IL-2 receptor expression and in proliferation. On the other hand, IL-2 recovery in the supernatants of O2-treated PBMC was always enhanced compared to the IL-2 control recovery after DNA synthesis was blocked in G1/S by mitomycin c, and the G0/G1 transition was protected by 2-ME. Furthermore, PHA-stimulated monocytes exposed to O2 produced more IL-1 than control cells. This enhanced IL-1 production was not modified by 2-ME. These results suggest that oxidative injury reduces the proliferation of PBMC by interfering with the cellular events that lead to the transition from the G0 to the G1 phase of the cell cycle. The protective effects of 2-ME suggest that thiol compounds have a critical role in the early events of the cell cycle. By contrast, exposure to O2 induced increases in the production of both IL-1 and IL-2 that may not be related to alterations in the thiol status of the cell.
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PMID:Mechanisms by which oxidative injury inhibits the proliferative response of human lymphocytes to PHA. Effect of the thiol compound 2-mercaptoethanol. 339 43