Prothymosin-α enhances HLA-DR antigen expression on monocytes from patients with multiple sclerosis

Baxevanis, Constantin N.; Anastasopoulos, Emmanuel; Reclos, George J.; Papamichail, Michail

doi:10.1016/0165-5728(90)90063-s

Cited by 33 publications

(25 citation statements)

References 21 publications

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“…ProTcz is a powerful immune response modifier. In in vitro studies, it has been demonstrated to potentiate CD4-positive cell proliferative responses to soluble proteins like keyhole limpet haemocyanin and ovalbumin [6], to enhance the human allogeneic and autologous mixed-lymphocyte reaction [3,4,6,7,20] and to increase the expression of major histocompatibility complex class II antigens on human monocytes [7]. These potentiating effects induced by ProTo~ are more apparent in deficient cellular immune responses such as those in patients with autoimmune diseases [3,4,20] and cancer (manuscript in preparation).…”

Section: Discussionmentioning

confidence: 99%

“…These potentiating effects induced by ProTo~ are more apparent in deficient cellular immune responses such as those in patients with autoimmune diseases [3,4,20] and cancer (manuscript in preparation). Upon analysing the mechanism of action of ProT~ in these in vitro cellular systems, we found that human monocytes after preincubation with ProTo~ (compared to non-treated monocytes) stimulate stronger T lymphocyte 149 proliferation in the mixed-lymphocyte reaction [6], express higher numbers of membrane HLA-DR antigens [7], and present effectively even extremely low amounts of antigen to T cells [6]. Finally, ProTc~ has been shown to increase the production of interleukin-2 and the expression of interleukin-2-specific receptors in antigen-activated T lymphocytes [5].…”

Section: Discussionmentioning

confidence: 99%

“…In in vitro experiments it was shown to potentiate normal donor T cell responses to cellular and soluble antigens and to increase the expression of major histocompatibility products on human monocytes [7]. The potentiating effect of ProTc~ was much more intense in deficient T cell responses from patients with autoimmune diseases [2][3][4]20].…”

Section: Introductionmentioning

confidence: 99%

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Promotion of murine antitumour activity by prothymosin α treatment: I. Induction of tumoricidal peritoneal cells producing high levels of tumour necrosis factor α

Papanastasiou¹,

Baxevanis²,

Papamichail³

1992

Cancer Immunol Immunother

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The effect of prothymosin alpha (ProT alpha) on the survival of DBA/2 mice inoculated with syngeneic tumour cells was studied. DBA/2 mice inoculated intraperitoneally (i.p.) with 2 x 10(5) syngeneic leukaemic L1210 cells developed ascites within 8-12 days and died 10-14 days later. Treatment with ProT alpha consistently inhibited the development of ascites in 20% of the treated animals and prolonged the survival of 40%-60% of the animals up to 70 days. The most effective treatment schedule of ProT alpha was 300 ng/mouse given i.p. at 2-day intervals for 3 weeks followed by a rest period of 7 days, prior to tumour cell inoculation. Peritoneal exudate (PE) cells collected from mice treated with the optimal dose of ProT alpha produced, in the absence of exogenous stimulus, six- to eightfold higher levels of tumour necrosis factor alpha (TNF alpha) than PE cells from control mice. Furthermore these cells exhibited cytotoxic activity against several tumour cell lines including the syngeneic L1210, the TNF-insensitive P815 mastocytoma, the human MOLT-4 lymphoblastic leukaemia, as well as the murine TNF-sensitive L929 fibroblast cell line. Kinetic studies revealed that both production of TNF alpha and tumoricidal activity peaked 7 days after the last injection of ProT alpha and were maintained at high levels over a period of 1 month. Injections with 150 ng ProT alpha slightly improved the survival of mice whereas higher (500 ng and 1000 ng) doses of ProT alpha and a wide range of thymosin alpha 1 doses remained without any effect. PE cells collected from these mice produced extremely low levels of TNF alpha and exhibited negligible tumoricidal activity. Our data demonstrate that ProT alpha has a protective effect in vivo against the growth of adoptively transferred tumour cells and suggest that this effect is, at least in part, mediated by ProT alpha-activated PE cells. These cells were demonstrated to produce high levels of TNF alpha in vitro and to exhibit activity against both TNF-sensitive and TNF-resistant cell lines.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Promotion of murine antitumour activity by prothymosin α treatment: I. Induction of tumoricidal peritoneal cells producing high levels of tumour necrosis factor α

Papanastasiou¹,

Baxevanis²,

Papamichail³

1992

Cancer Immunol Immunother

Self Cite

View full text Add to dashboard Cite

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“…It is widely distributed in human cells [13], protects against infection from Candida albicans [14], induces the enhanced secretion of interleukin [15] and migration inhibition factor [16], activates monocytes and T-lymphocytes and is a strong immunomodulator [17].…”

Section: Introductionmentioning

confidence: 99%

The effect of various Prothymosin α fragments on the crystal growth of hydroxyapatite in aqueous solution

Koutsopoulos¹,

Barlos²,

Gatos³

et al. 2004

Journal of Crystal Growth

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“…It enhances the HLA-DR expression on monocytes from patients with multiple sclerosis, resulting in the restoration of the deficient autologous MLR (15). The depressed autologous and allogeneic MLR in patients with systemic lupus erythematosus can be enhanced in the presence of ProT (16).…”

mentioning

confidence: 99%

Prothymosin α Lacking the Nuclear Localization Signal as an Effective Gene Therapeutic Strategy in Collagen-Induced Arthritis

Shiau¹,

Chen²,

Chang³

et al. 2007

The Journal of Immunology

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Prothymosin α (ProT) is regulated by c-Myc, an oncoprotein overexpressed in synovium of rheumatoid arthritis, and is associated with cell proliferation. However, ProT also exerts immunomodulatory activities. The growth-promoting activity of ProT can be abolished by deleting its nuclear localization signal (NLS). In this study, we showed that AdProTΔNLS, an adenoviral vector encoding ProT lacking the NLS, did not enhance the proliferation of synovial fibroblasts. AdProTΔNLS treatment abolished the up-regulation of the MIP-1α promoter activity induced by TNF-α in synovial fibroblasts. AdProTΔNLS suppressed macrophage chemotaxis and reduced macrophage infiltration into the ankle joints in rats with collagen-induced arthritis (CIA). Neutralization test confirmed the involvement of MIP-1α in macrophage chemotaxis. Administration of AdProTΔNLS reduced the severity of CIA in the clinical, radiographic, and histological aspects. The levels of TNF-α (mean ± SEM, 1261.9 ± 107.9 vs 2880.1 ± 561.4 pg/mg total protein; p < 0.05), IL-1β (56.8 ± 8.0 vs 109.2 ± 4.9 pg/mg total protein; p < 0.01), and MIP-1α (41.7 ± 3.6 vs 55.2 ± 1.1 pg/mg total protein; p < 0.05) in the ankle joints were lower in the AdProTΔNLS-treated rats with CIA than those in their control counterparts. In the AdProTΔNLS-treated ankle joints, matrix metalloproteinase-9 expression was decreased by 40% and infiltrating macrophages reduced by 50%. Our results demonstrate that intra-articular delivery of AdProTΔNLS significantly ameliorated the clinical course of CIA in rats. This study is the first to suggest that ProT lacking the NLS may have therapeutic potential for the management of rheumatoid arthritis.

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Prothymosin-α enhances HLA-DR antigen expression on monocytes from patients with multiple sclerosis

Cited by 33 publications

References 21 publications

Promotion of murine antitumour activity by prothymosin α treatment: I. Induction of tumoricidal peritoneal cells producing high levels of tumour necrosis factor α

Promotion of murine antitumour activity by prothymosin α treatment: I. Induction of tumoricidal peritoneal cells producing high levels of tumour necrosis factor α

The effect of various Prothymosin α fragments on the crystal growth of hydroxyapatite in aqueous solution

Prothymosin α Lacking the Nuclear Localization Signal as an Effective Gene Therapeutic Strategy in Collagen-Induced Arthritis

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