Linoleic Acid as an Immunosuppressive Agent

Weyman, Christine; Belin, J; Smith, Anthony D.; Thompson, Ronald G.

doi:10.1016/s0140-6736(75)92977-3

Cited by 59 publications

(14 citation statements)

References 3 publications

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“…An endometrial cancer cell line shows 23% growth inhibition after 72 h. The finding that OA negates the effect of SA agrees with the results of Weyman et al (1975) Comparison of control (0) (King & Cuatrecasas, 1982;Kawamoto et al, 1983). Cell lines expressing only a single class of EGF receptor are also described (Mummery et al, 1983;Fabbro et al, 1986).…”

Section: Resultssupporting

confidence: 75%

Fatty acid control of growth of human cervical and endometrial cancer cells

Gleeson

Ayub²,

Wright³

et al. 1990

Br J Cancer

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Summary Stearic acid and iodo-stearic acid inhibited cell growth in a cervical cancer cell line (HOG-1) in a dose-related manner, with a half maximal effect at 50 JAM stearic acid. Addition of oleic acid abrogated the effect of stearic acid. EGF-stimulated DNA synthesis and growth of HOG-1 cells was inhibited in the presence of stearic acid without any apparent effect on EGF receptor number or affinity.Many reports have demonstrated effects of fatty acids on cell growth, showing growth stimulation in normal and neoplastic cells (Wicha et al., 1979), growth inhibition without toxic effects (Williams et al., 1974) and cytocidal effects (Siegel et al., 1987). In general, saturated fatty acids (SFA) inhibit cell growth (Doi et al., 1978), whereas unsaturated fatty acids (USFA) stimulate growth (Wicha et al., 1979).These effects may be explained by the alteration in functional properties of cell membranes caused by changing their fatty acid content (Spector & Burns, 1987). The function of membrane proteins can be modified by the fluidity or microviscosity of surrounding lipids, which may effect the conformation and availability of membrane receptors (Shinitzky, 1984). Mobility within the plane of the cell membrane is necessary for the activation of the epidermal growth factor (EGF) receptor (Schlessinger, 1988), but there is no reported work on the possible effects of fatty acid modulation of cell membranes on EGF receptor function.Stearic acid (SA) has been shown to inhibit growth of normal and neoplastic rat mammary epithelial cells (Wicha et al., 1979). As effects of fatty acids on neoplasic of the uterine cervix have not been investigated, this work examines the effect of stearic acid (SA) and 9 (10)-iodostearic acid (ISA), which may strongly influence membrane fluidity (Apostolov, 1980), on a human cervical cancer cell line. Fatty acid membrane modulation may affect the characteristics of receptor proteins and, as the importance of EGF and its receptor in the growth of gynaecological tumours has been suggested by Cowley et al. ( ), Kudlow et al. (1986, Sainsbury et al. (1987), Singletary et al. (1987) and Wu et al. (1981), we therefore also investigated the effect of SA on EGFstimulated growth and receptor characteristics in HOG-1 cells. Materials and methodsMaintenance of cells in culture HOG-1 cells were maintained in Dulbecco's Modified Eagle Medium (DMEM) plus 10% heat inactivated fetal calf serum (FCS) in 5% CO2 at 37°C. Gentamicin (640 1tg per 100 ml) and glutamine (29.2 mg per 100 ml) were added to the medium. As a preliminary step to each experiment, cells were pre-incubated in DMEM containing 10% delipidised fetal calf serum (DLS) for three days. DLS was prepared by adding 50 ml of FCS to 500 ml of 1:1 ethanol:acetone. This was stirred for 4 h and filtered through Watman no. 1 paper with cold ether. The precipitate was dried, reconstituted in deionised water, and the resulting serum was filter sterilised. Growth of HOG-I cells in serum-free defined medium Some experiments were conducted in serum-free ch...

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Section: Resultssupporting

confidence: 75%

Fatty acid control of growth of human cervical and endometrial cancer cells

Gleeson

Ayub²,

Wright³

et al. 1990

Br J Cancer

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“…Therefore, it can be speculated that the AA thus liberated is taken up by bystander cells to be metabolized to eicosanoids, representing a particular transcellular pathway for AA metabolism. In addition, it has been shown that AA affects leukocyte adhesion by suppressing the expression of adhesion molecules on endothelial cells (45)(46)(47), activates NADPH oxidase (48 -50), and exerts direct effects on phagocyte H ϩ and Ca 2ϩ ion flux (51)(52)(53)(54). These actions may contribute to propagation of inflammatory processes, and the secreted AA-S100A8/A9 complex may here be involved, probably as the shuttle protein to reach target cells.…”

Section: Discussionmentioning

confidence: 99%

The Two Calcium-binding Proteins, S100A8 and S100A9, Are Involved in the Metabolism of Arachidonic acid in Human Neutrophils

Kerkhoff¹,

Klempt²,

Kaever³

et al. 1999

Journal of Biological Chemistry

154

160

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Recently, we identified the two myeloid related protein-8 (MRP8) (S100A8) and MRP14 (S100A9) as fatty acid-binding proteins (Klempt, M., Melkonyan, H., Nacken, W., Wiesmann, D., Holtkemper, U., and Sorg, C. (1997) FEBS Lett. 408, 81-84). Here we present data that the S100A8/A9 protein complex represents the exclusive arachidonic acid-binding proteins in human neutrophils. Binding and competition studies revealed evidence that (i) fatty acid binding was dependent on the calcium concentration; (ii) fatty acid binding was specific for the protein complex formed by S100A8 and S100A9, whereas the individual components were unable to bind fatty acids; (iii) exclusively polyunsaturated fatty acids were bound by S100A8/A9, whereas saturated (palmitic acid, stearic acid) and monounsaturated fatty acids (oleic acid) as well as arachidonic acid-derived eicosanoids (15-hydroxyeicosatetraenoic acid, prostaglandin E 2 , thromboxane B 2 , leukotriene B 4 ) were poor competitors. Stimulation of neutrophil-like HL-60 cells with phorbol 12-myristate 13-acetate led to the secretion of S100A8/A9 protein complex, which carried the released arachidonic acid. When elevation of intracellular calcium level was induced by A23187, release of arachidonic acid occurred without secretion of S100A8/A9. In view of the unusual abundance in neutrophilic cytosol (approximately 40% of cytosolic protein) our findings assign an important role for S100A8/A9 as mediator between calcium signaling and arachidonic acid effects. Further investigations have to explore the exact function of the S100A8/A9-arachidonic acid complex both inside and outside of neutrophils.The two myeloid-related proteins, MRP8 and MRP14, belong to the S100 family of calcium-binding proteins (for review, see Refs. 1-4). They are composed of two distinct EF-hands flanked by hydrophobic regions at either terminus and separated by a central hinge region, and they form a heterodimeric complex in a Ca 2ϩ -dependent manner. Heizmann and Schä fer (5) proposed a new logical nomenclature for these genes based on the physical arrangement of the genes encoding the S100 family on chromosome 1q21. According to this nomenclature, MRP8 and MRP14 are referred to as S100A8 and S100A9, respectively.Both proteins are expressed in circulating neutrophils and monocytes but are absent in normal tissue macrophages and lymphocytes (6 -9). Under chronic inflammatory conditions, such as psoriasis and malignant disorders, they are also expressed in the epidermis (10 -12). S100A8 and S100A9 are predominantly localized in the cytoplasm. Upon elevation of the intracellular calcium level they are translocated from the cytosol to cytoskeleton and to plasma membrane (13). At a later time point, they appear as noncovalently associated S100A8/A9 heterodimers on the surface of monocytes (14). The mechanism by which the S100A8/A9 heterodimer penetrates the plasma membrane and how the S100A8/A9 protein complex is anchored into the cell membrane, remains unclear since both proteins lack a transmembrane region. Upon th...

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“…This has perhaps to do with the ratio of saturated to unsaturated lipids in the diet. A related study by Weyman et al (1975) indicated that the ratio of saturated to unsaturated fatty acids may determine the ultimate degree of inhibition on lymphocyte re sponse.…”

Section: Discussionmentioning

confidence: 99%