The production of nitric oxide in EL4 lymphoma cells overexpressing growth hormone

Arnold, Robyn; Weigent, Douglas A.

doi:10.1016/s0165-5728(02)00420-4

Cited by 20 publications

(23 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, measurements of NOS activity in tumors taken from the eNOS and iNOS knockout mice demonstrated that most of this NOS activity must have been in the tumor cells, as opposed to host cells present in the tumor, such as infiltrating immune cells and endothelial cells. The presence of eNOS, nNOS, and iNOS in EL-4 cells has also been demonstrated by Western blotting (6). Measurements on liver extracts, in the presence of the isoform-selective inhibitors, confirmed the NOS status of the eNOS and iNOS knockout mice (Fig.…”

Section: Involvement Of Tumor-derived No In Immune Rejectionsupporting

confidence: 59%

“…There is evidence that NO is involved in both tumor angiogenesis and in immune cell killing of tumor cells and, therefore, can have both positive and negative effects on tumor progression. At relatively low concentrations, NO can protect tumor cells from apoptosis (4,5), including in the EL-4 cell line used in this study (6), stimulate tumor angiogenesis, and increase tumor blood flow (7,8), thus promoting tumor growth; whereas at higher levels, it can induce apoptosis and arrest tumor growth (9 -11). In tumor cells transfected with vectors expressing iNOS, tumor growth and metastatic potential were shown to be dependent on both the level of NO produced and the presence of wild-type p53 (12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Tumor Cell-Derived Nitric Oxide Is Involved in the Immune-Rejection of an Immunogenic Murine Lymphoma

Dyke

Moore

et al. 2004

Cancer Research

View full text Add to dashboard Cite

The roles played by host-derived nitric oxide (NO) in the growth and subsequent immune rejection of a immunogenic murine lymphoma were investigated by growing the tumor in mice in which the gene for either inducible NO synthase (iNOS) or endothelial NOS (eNOS) had been ablated. This showed that NO from tumor-infiltrating host cells had no significant effect on either tumor growth or immune rejection, although measurements of tumor nitrite levels and protein nitration showed that there had been significant NO production in the rejected tumors, in both the eNOS and iNOS knockout mice. Inhibition of both tumor and host NOS activities, with an iNOS-selective inhibitor (1400W), a nonselective NOS inhibitor [N-nitro-L-arginine methyl ester (L-NAME)], or scavenging NO with a ruthenium-based scavenger, significantly delayed tumor rejection, while having no appreciable effect on tumor growth. Incubation of tumor cells with medium taken from cultured splenocytes, that had been isolated from immunized animals and activated by incubating them with irradiated tumor cells, resulted in an increase in tumor cell NOS activity and an increase in tumor cell apoptosis, which could be inhibited using L-NAME. We propose that, during the immune rejection of this tumor model, there is induction of tumor NOS activity by cytokines secreted by activated lymphocytes within the tumor and that this results in increased levels of tumor NO that induce tumor cell apoptosis and facilitate immune rejection of the tumor.

show abstract

Section: Involvement Of Tumor-derived No In Immune Rejectionsupporting

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Tumor Cell-Derived Nitric Oxide Is Involved in the Immune-Rejection of an Immunogenic Murine Lymphoma

Dyke

Moore

et al. 2004

Cancer Research

View full text Add to dashboard Cite

show abstract

“…For in vitro experiments, each fusion construct and controls were transfected at least 4 times, and each transfection was done in triplicate as previously described [20]. All experiments were repeated at least 3 times.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to the large quantities of ROI produced by phagocytes to kill invading microorganisms, a variety of nonphagocytic cells are also capable of ROI production [19]. In this regard, we have previously shown an increase in the production of NO [20,21] and a decrease in the production of superoxide [22] in EL4 lymphoma cells overexpressing GH (GHo). The increase in NO was observed along with an increase in the expression of inducible nitric oxide synthase (iNOS) while the decrease in superoxide was accompanied by a reduction in the activity of CYP 2E1.…”

Section: Introductionmentioning

confidence: 99%

“…The increase in NO was observed along with an increase in the expression of inducible nitric oxide synthase (iNOS) while the decrease in superoxide was accompanied by a reduction in the activity of CYP 2E1. Further, the GHo cells exhibited an increased mitochondrial membrane potential, an effect which could be blocked by prior treatment with N Gmonomethyl-L-arginine (L-NMMA), a NOS inhibitor [20][21][22].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Inhibition of Apoptosis in EL4 Lymphoma Cells Overexpressing Growth Hormone

Arnold¹,

Weigent²

2004

Neuroimmunomodulation

Self Cite

View full text Add to dashboard Cite

The antiapoptotic action of exogenous growth hormone (GH) has been reported for several lymphoid cell lines; however, the potential role of endogenous GH in apoptosis has not been thoroughly investigated. This study was designed to investigate the effects of endogenous GH on apoptosis induced by methyl methanesulfonate (MMS) in a T cell lymphoma overexpressing GH (GHo). The results of these experiments have shown that in EL4 lymphoma cells, overexpression of GH sustained viability after exposure to MMS compared to control cells. The extent of DNA fragmentation measured by ladder formation on agarose gels was reduced in GHo cells following treatment with MMS, when compared to control cells. Adding exogenous GH to control cells and treatment of GHo cells with antibodies to GH had no effect on MMS-induced DNA ladder formation. In further studies, DNA microarray analysis suggested a marked decrease in the constitutive expression of bax, BAD, and caspases 3, 8, and 9 in GHo cells compared to controls. In addition, after treatment with MMS, the activities of caspases 2, 3, 6, 8, and 9 were all lower than control in GHo cells. Western blot analysis detected an increase in Bcl-2 while the levels of nuclear factor kappa B (NFĸB) remained unchanged in GHo cells. Treatment of EL4 cells with antisense deoxyoligonucleotides to GH and specific inhibitors of NFĸB (SN-50) increased DNA fragmentation. GHo cells show increased levels of phosphorylated Akt and GSK-3, suggesting inactivation of this proapoptotic protein. The results, taken together with our previous data which showed increased nitric oxide formation in GHo cells, suggest a possible mechanism for the antiapoptotic effects of endogenous GH through the production of nitric oxide and support the idea that endogenous GH may play an important role in the survival of lymphocytes exposed to stressful stimuli.

show abstract

Bidirectional Communication Between the Brain and the Immune System

Weigent¹,

Blalock²

Neuroimmunology of Sleep

View full text Add to dashboard Cite

The production of nitric oxide in EL4 lymphoma cells overexpressing growth hormone

Cited by 20 publications

References 82 publications

Tumor Cell-Derived Nitric Oxide Is Involved in the Immune-Rejection of an Immunogenic Murine Lymphoma

Tumor Cell-Derived Nitric Oxide Is Involved in the Immune-Rejection of an Immunogenic Murine Lymphoma

The Inhibition of Apoptosis in EL4 Lymphoma Cells Overexpressing Growth Hormone

Bidirectional Communication Between the Brain and the Immune System

Contact Info

Product

Resources

About