Esther Melgarejo

Monocyte chemoattractant protein-1: a key mediator in inflammatory processes.

Monocyte chemoattractant protein-1 (MCP-1) is a potent chemoattractant for monocytes and macrophages to areas of inflammation. MCP-1 is a prototypical chemokine subject to coordinated regulation by immunomodulatory agents. Since MCP-1 is implicated in multiple inflammatory diseases, it is a potential target for the treatment of these disorders. In this review, we will provide background information and summarize the MCP-1 structure and signaling pathways. Its involvement in multiple diseases, such as tumour development, atherogenesis and rare autoimmune diseases is also revised.

Epigallocatechin gallate reduces human monocyte mobility and adhesion in vitro

Background and purpose:  Monocytes/macrophages are an important population of immune inflammatory cells that have diverse effector functions in which their mobility and adhesion play a very relevant role. Epigallocatechin gallate (EGCG), a major component of green tea, has been reported to have anti‐allergic and anti‐inflammatory activities, but its effects on monocytes remain to be determined. Here we investigated the effects of EGCG on the migration and adhesion of monocytes.

(—)-Epigallocatechin-3-gallate interferes with mast cell adhesiveness, migration and its potential to recruit monocytes

Abstract.Mast cells are multipotent effector cells of the immune system. They are able to induce and enhance angiogenesis via multiple pathways. (—)-Epigallocatechin-3-gallate (EGCG), a major component of green tea and a putative chemopreventive agent, was reported to inhibit tumor invasion and angiogenesis, processes that are essential for tumor growth and metastasis. Using the human mast cell line HMC-1 and commercial cDNA macroarrays, we evaluated the effect of EGCG on the expression of angiogenesis-related genes. Our data show that among other effects, EGCG treatment reduces expression of two integrins (α5 and β3) and a chemokine (MCP1), resulting in a lower adhesion of mast cells associated with a decreased potential to produce signals eliciting monocyte recruitment. These effects on gene expression levels are functionally validated by showing inhibitory effects in adhesion, aggregation, migration and recruitment assays.

Targeting of histamine producing cells by EGCG: a green dart against inflammation?

The human body is made of some 250 different cell types. From them, only a small subset of cell types is able to produce histamine. They include some neurons, enterochromaffin-like cells, gastrin-containing cells, mast cells, basophils, and monocytes/macrophages, among others. In spite of the reduced number of these histamine-producing cell types, they are involved in very different physiological processes. Their deregulation is related with many highly prevalent, as well as emergent and rare diseases, mainly those described as inflammation-dependent pathologies, including mastocytosis, basophilic leukemia, gastric ulcer, Crohn disease, and other inflammatory bowel diseases. Furthermore, oncogenic transformation switches some non-histamine-producing cells to a histamine producing phenotype. This is the case of melanoma, small cell lung carcinoma, and several types of neuroendocrine tumors. The bioactive compound epigallocatechin-3-gallate (EGCG), a major component of green tea, has been shown to target histamine-producing cells producing great alterations in their behavior, with relevant effects on their proliferative potential, as well as their adhesion, migration, and invasion potentials. In fact, EGCG has been shown to have potent anti-inflammatory, anti-tumoral, and anti-angiogenic effects and to be a potent inhibitor of the histamine-producing enzyme, histidine decarboxylase. Herein, we review the many specific effects of EGCG on concrete molecular targets of histamine-producing cells and discuss the relevance of these data to support the potential therapeutic interest of this compound to treat inflammation-dependent diseases.

Targeting polyamines and biogenic amines by green tea epigallocatechin-3-gallate.

Biogenic amines and polyamines are organic polycations derived from aromatic or cationic amino acids. They exert pleiotropic effects, more related to intercellular communication in the case of biogenic amines, and to intracellular signaling in the case of polyamines. The bioactive compound epigallocatechin-3-gallate (EGCG), a major component of green tea, has been shown to target key enzyme of biogenic amine and polyamine metabolic pathways. Herein, we review the specific effects of EGCG on concrete molecular targets of both biogenic amine and polyamine metabolic pathways, and discuss the relevance of these data to support the potential therapeutic interest of this compound.

Histamine: an undercover agent in multiple rare diseases?

Histamine is a biogenic amine performing pleiotropic effects in humans, involving tasks within the immune and neuroendocrine systems, neurotransmission, gastric secretion, cell life and death, and development. It is the product of the histidine decarboxylase activity, and its effects are mainly mediated through four different G‐protein coupled receptors. Thus, histamine‐related effects are the results of highly interconnected and tissue‐specific signalling networks. Consequently, alterations in histamine‐related factors could be an important part in the cause of multiple rare/orphan diseases. Bearing this hypothesis in mind, more than 25 rare diseases related to histamine physiopathology have been identified using a computationally assisted text mining approach. These newly integrated data will provide insight to elucidate the molecular causes of these rare diseases. The data can also help in devising new intervention strategies for personalized medicine for multiple rare diseases.

The Brominated Compound Aeroplysinin-1 Inhibits Proliferation and the Expression of Key Pro- Inflammatory Molecules in Human Endothelial and Monocyte Cells

Aeroplysinin-1 is a brominated antibiotic used by some sponges for defense against bacterial pathogen invasion. Aeroplysinin-1 has a wide spectrum of anti-tumoral action and behaves as a potent anti-angiogenic compound for bovine aortic endothelial cells. In this study, we demonstrate anti-angiogenic effects of aeroplysinin-1 on human endothelial cells. Furthermore, the response of angiogenesis related genes to aeroplysinin-1 treatment was studied in human endothelial cells by using gene arrays. The major changes were observed in thrombospondin 1 (TSP-1) and monocyte chemoattractant protein-1 (MCP-1), both of which were down-regulated. These inhibitory effects of aeroplysinin-1 were confirmed by using independent experimental approaches. To have a deeper insight on the anti-inflammatory effects of aeroplysinin-1 in endothelial cells, cytokine arrays were also used. This experimental approach confirmed effects on MCP-1 and TSP-1 and showed down-regulation of several other cytokines. Western blotting experiments confirmed down-regulation of ELTD1 (EGF, latrophilin and seven transmembrane domain-containing protein 1), interleukin 1α and matrix metalloproteinase 1 (MMP-1). These results along with our observation of a dramatic inhibitory effect of aeroplysinin-1 on cyclooxygenase-2 protein expression levels in endothelial cells and a human monocyte cell line suggest that aeroplysinin-1 could be a novel anti-inflammatory compound with potential pharmacological interest.

Development of an expression macroarray for amine metabolism-related genes

Summary.Cationic amino acids are the precursors of biogenic amines, histamine from histidine, and putrescine, spermidine and spermine from arginine/ornithine (and methionine), as well as nitric oxide. These amines play important biological roles in inter- and intracellular signaling mechanisms related to inflammation, cell proliferation and neurotransmission. Biochemical and epidemiological relationships between arginine-derived products and histamine have been reported to play important roles in physiopathological problems. In this communication, we describe the construction of an expression macroarray containing more than 30 human probes for most of the key proteins involved in biogenic amines metabolisms, as well as other inflammation- and proliferation-related probes. The array has been validated on human mast HMC-1 cells. On this model, we have got further support for an inverse correlation between polyamine and histamine synthesis previously observed on murine basophilic models. These tools should also be helpful to understand the amine roles in many other inflammatory and neoplastic pathologies.

Effects of photoacclimation on plasma membrane ferricyanide reductase from the rhodophyta Gracilaria tenuistipitata

The red macroalga Gracilaria tenuistipitata has a plasma membrane redox system easily assayed as a ferricyanide reductase (EC 1.6.99.13) activity. This activity is associated with acidification of the medium and is modulated by light conditions. G. tenuistipitata thalli adapt to light conditions by changes affecting their morphology, physiology and biochemistry. Thalli adapted to high photon fluence rates exhibited lower ferricyanide reductase activity than those adapted to darkness or low irradiance (40 mmol photon m 2 s 1 ). When thalli were changed from low to high irradiance (500 mmol photons m 2 s 1 ), there was a continuous decrease in ferricyanide reductase activity with time. When these thalli were changed to darkness, they recovered to control values of ferricyanide reductase activity after a 24 h additional incubation. Adaption of thalli to different qualities of light also produced significant changes in their ferricyanide reductase activity: under the same low irradiance (40 mmol photons m 2 s 1 ), thalli exposed for two or more weeks to blue or red light exhibited higher ferricyanide reductase activity levels than those exposed to white light; after four weeks of culture, thalli under blue light had higher ferricyanide reductase activity levels than those under red light. It is concluded that the differences in ferricyanide reductase activity observed under different light conditions are the result of acclimation and that this activity could play a relevant role in G. tenuistipitata bioenergetics. # 2002 Elsevier Science Ireland Ltd. All rights reserved.