Alpha-, beta- and kappa-caseins inhibit the proliferation of the myeloid cell lines 32D cl3 and WEHI-3 and exhibit different differentiation properties

Ramos‐Mandujano, Gerardo; Weiss‐Steider, Benny; Melo, B.; Córdova, Yolanda; Ledesma‐Martínez, Edgar; Bustos, Silvina Odete; Silvestre, Óscar F.; Aguiñiga, Itzen; Sosa, N.; Martı́nez, Ignacio; Sánchez, Lourdes; Garcia, Andy; Santiago‐Osorio, Edelmiro

doi:10.1016/j.imbio.2007.07.004

Cited by 13 publications

(21 citation statements)

References 23 publications

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“…There is ongoing research about the stimuli controlling GM-CSF expression (34). Interestingly, bovine caseins were shown to induce the secretion of M-CSF in murine myeloid cells (18). The present data demonstrated that human CSN1S1 leads to increased expression and secretion of GM-CSF in human monocytic cells and monocytes.…”

Section: Discussionsupporting

confidence: 51%

“…Polypeptides in milk may be degraded by proteases within milk and the digestive tract or survive the digestive process in an intact form (1). Research has focused on fermented fragments and identified a number of immunomodulatory effects (7)(8)(9)(10)(11), such as the modulation of leukocyte adhesion (12), chemotactic properties (13)(14)(15)(16), inhibition of cell growth (17,18), modulation of the innate immune response of intestinal cells (19), amelioration of experimental inflammation (20), and chaperone-like activities (21). Most of these investigations were focused on bovine casein-derived peptides.…”

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confidence: 99%

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Casein α s1 Is Expressed by Human Monocytes and Upregulates the Production of GM-CSF via p38 MAPK

Vordenbäumen

Braukmann

Petermann

et al. 2011

The Journal of Immunology

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Caseins are major constituents of mammalian milks that are thought to be exclusively expressed in mammary glands and to function primarily as a protein source, as well as to ameliorate intestinal calcium uptake. In addition, proinflammatory and immunomodulatory properties have been reported for bovine caseins. Our aim was to investigate whether human casein α s1 (CSN1S1) is expressed outside the mammary gland and possesses immunomodulatory functions in humans as well. For this purpose, CSN1S1 mRNA was detected in primary human monocytes and CD4+ and CD8+ T cells, but not in CD19+ B cells. CSN1S1 protein was traceable in supernatants of cultured primary human CD14+ monocytes by ELISA. Similarly, CSN1S1 mRNA and protein were detected in the human monocytic cell lines HL60, U937, and THP1 but not in Mono Mac 6 cells. Moreover, permeabilized human monocytes and HL60 cells could be stained by immunofluorescence, indicating intracellular expression. Recombinant human CSN1S1 was bound to the surface of Mono Mac 6 cells and upregulated the expression of GM-CSF mRNA in primary human monocytes and Mono Mac 6 cells in a time- and concentration-dependent manner. A similar increase in GM-CSF protein was found in the culture supernatants. CSN1S1-dependent upregulation of GM-CSF was specifically blocked by the addition of the p38 MAPK inhibitor ML3403. Our results indicated that human CSN1S1 may possess an immunomodulatory role beyond its nutritional function in milk. It is expressed in human monocytes and stimulates the expression of the proinflammatory cytokine GM-CSF.

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Section: Discussionsupporting

confidence: 51%

mentioning

confidence: 99%

Casein α s1 Is Expressed by Human Monocytes and Upregulates the Production of GM-CSF via p38 MAPK

Vordenbäumen

Braukmann

Petermann

et al. 2011

The Journal of Immunology

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“…1 mg/ml, NaCN exerted the strongest growth inhibition on 32Dcl3 cells but the inhibition was not as potent on WEHI-3 cell growth. This variation in findings may be explained by the different protein concentrations and the different cell lines used in these studies (Hagiwara et al 1995;Ramos-Mandujano et al 2008). In addition, the types and sources of peptide can have individual effects on cells (Hagiwara et al 1995 ;Meisel & Gü nther, 1998).…”

Section: Discussionmentioning

confidence: 96%

“…Recently, Ramos-Mandujano et al (2008) showed that NaCN and its individual casein components displayed different inhibitory characteristics on the proliferation of 32Dcl3 and WEHI-3 myeloid cells. At 0 .…”

Section: Discussionmentioning

confidence: 99%

Growth inhibitory effects of casein hydrolysates on human cancer cell lines

Phelan

Aherne

O’Sullivan

et al. 2010

Journal of Dairy Research

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The aim of this study was to investigate the effects of unhydrolysed/intact casein and eight different sodium casein hydrolysates (a-h) on the viability and growth of human cancer cell lines. Both human Jurkat T cells and Caco-2 cells were incubated with increasing concentrations of the test compounds (0 . 5-10 % v/v) for 24 h. Cell viability was assessed using the MTT, lactate dehydrogenase (LDH) release and Trypan Blue assays. Cell growth was monitored using the MTT, Trypan Blue and Bromodeoxyuridine (BrdU) proliferation assays. Casein hydrolysates b, c and f had an inhibitory effect on the viability and growth of both cell lines. The casein hydrolysates did not negatively affect the membrane integrity of both Jurkat and Caco-2 cells. In Jurkat cells hydrolysates a and h had an inhibitory effect on DNA synthesis after 24 h, while in Caco-2 cells DNA synthesis was not affected. In conclusion, we found that the different casein hydrolysates had cell-specific effects which target particular functions within the cell. Overall, casein hydrolysates had no effect on membrane integrity while they had varied effects on mitochondrial activity and DNA synthesis in the different cell lines.

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“…In a previous study, we showed that casein inhibits the proliferation of the normal mouse myeloid cell line 32D by inducing its differentiation into the monocyte-macrophage lineage (6). Additionally, casein has been shown to inhibit the proliferation of several leukaemia cell lines (7).…”

Section: Introductionmentioning

confidence: 99%

Casein induces the proliferation of bone marrow mononuclear cells, apoptosis of WEHI-3 leukaemic cells and increased survival in a leukaemia mouse model

et al. 2012

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Alpha-, beta- and kappa-caseins inhibit the proliferation of the myeloid cell lines 32D cl3 and WEHI-3 and exhibit different differentiation properties

Cited by 13 publications

References 23 publications

Casein α s1 Is Expressed by Human Monocytes and Upregulates the Production of GM-CSF via p38 MAPK

Casein α s1 Is Expressed by Human Monocytes and Upregulates the Production of GM-CSF via p38 MAPK

Growth inhibitory effects of casein hydrolysates on human cancer cell lines

Casein induces the proliferation of bone marrow mononuclear cells, apoptosis of WEHI-3 leukaemic cells and increased survival in a leukaemia mouse model

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