Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Macrophages generally constitute a major component of tumor stroma, and possess either tumor growth promoting or inhibiting capabilities. Classically activated macrophages exert cytotoxicity and produce inflammatory cytokines, which limits tumor growth. By contrast, alternatively activated or M2 macrophages induce tumor progression by stimulating angiogenesis and proliferation. Previously we showed that resident macrophages control metastatic spread of coloncarcinoma cells in liver and peritoneal tumor models. However, it is proposed that newly recruited macrophages develop into tumor-associated M2 macrophages, as they are exposed to a microenvironment that favors alternative activation. Previously we showed that monocyte migration was diminished after flavonoid treatment in an experimental autoimmune encephalomyelitis animal model. In the present study, we investigated the role of newly recruited macrophages in colon carcinoma development, by using the flavonoids rutin and luteolin to reduce monocyte migration into peritoneal tumors. Increased tumor development was observed in animals that were treated with rutin and luteolin. Immunohistochemical analyses showed that the number of ED2(+) resident macrophages was normal in tumors of animals that received rutin and luteolin treatment. However, the number of ED1(+) cells (marker immature macrophages) was reduced, indicating decreased macrophage recruitment. Thus, inhibition of monocyte migration promotes tumor growth, supporting that not only resident, but also newly recruited macrophages limit peritoneal colon carcinoma metastases development.
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PMID:Tumor infiltrating macrophages reduce development of peritoneal colorectal carcinoma metastases. 1818 56

CCL2 is a key CC chemokine that has been implicated in a variety of inflammatory autoimmune diseases and in tumor progression and it is therefore an important target for therapeutic intervention in these diseases. Soluble receptor-based therapy is a known approach for neutralizing the in vivo functions of soluble mediators. Owing to the complexity of seven-transmembrane G protein-coupled receptors, efforts to generate neutralizing soluble chemokine receptors have so far failed. We developed a strategy that is based on the generation of short recombinant proteins encoding different segments of a G protein-coupled receptor, and tested the ability of each of them to bind and neutralize its target chemokine. We show that a fusion protein comprised of as few as 20 aa of the third extracellular (E3) domain of the CCL2 receptor, stabilized by the IgG H chain Fc domain (E3-IgG or BL-2030), selectively binds CCL2 and CCL16 and effectively neutralizes their biological activities. More importantly, E3-IgG (BL-2030) could effectively suppress the in vivo biological activity of CCL2, attenuating ongoing experimental autoimmune encephalomyelitis, as well as the development of human prostate tumor in SCID mice.
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PMID:A novel recombinant fusion protein encoding a 20-amino acid residue of the third extracellular (E3) domain of CCR2 neutralizes the biological activity of CCL2. 1953 19

Extracellular matrix metalloproteinase inducer (EMMPRIN, CD147) is a member of the Ig superfamily, with various physiological roles including the induction of matrix metalloproteinases (MMPs), leukocyte activation, and tumor progression. In this study, we illustrate a novel involvement of EMMPRIN in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). We found EMMPRIN levels to be upregulated on peripheral leukocytes before onset of EAE clinical signs and on infiltrating leukocytes and resident cells within the CNS in symptomatic mice. In EAE brain sections, EMMPRIN expression was localized with MMP-9 protein and activity. The increased EMMPRIN level was also characteristic of brain samples from MS subjects, particularly in plaque-containing areas. To evaluate the implications of elevated EMMPRIN levels, we treated EAE mice with an EMMPRIN function-blocking antibody and found reduced EAE clinical severity accompanied by decreased CNS parenchymal infiltration of leukocytes. Amelioration of EAE clinical signs by the anti-EMMPRIN antibody was critically dependent on its administration around the period of onset of clinical signs, which is typically associated with significant influx of leukocytes into the CNS. Moreover, the reduction in disease severity in anti-EMMPRIN-treated mice was associated with diminished MMP proteolytic activity at the glia limitans, the final barrier before parenchymal infiltration of leukocytes. Together, our results are the first to emphasize a role for EMMPRIN in MS and EAE, whereby EMMPRIN regulates leukocyte trafficking through increasing MMP activity. These results identify EMMPRIN as a novel therapeutic target in MS.
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PMID:EMMPRIN: a novel regulator of leukocyte transmigration into the CNS in multiple sclerosis and experimental autoimmune encephalomyelitis. 2122 76

Hepatocyte growth factor (HGF) signaling via the MET receptor is essential for embryonic development and tissue repair. On the other hand, deregulated MET signaling promotes tumor progression in diverse types of cancers. Even though oncogenic MET signaling remains the major research focus, the HGF-MET axis has also been implicated in diverse aspects of immune cell development and functions. In the presence of other hematopoietic growth factors, HGF promotes the development of erythroid, myeloid and lymphoid lineage cells and thrombocytes. In monocytes and macrophages responding to inflammatory stimuli, induction of autocrine HGF-MET signaling can contribute to tissue repair via stimulating anti-inflammatory cytokine production. HGF-MET signaling can also modulate adaptive immune response by facilitating the migration of Langerhans cells and dendritic cells to draining lymph nodes. However, MET signaling has also been shown to induce tolerogenic dendritic cells in mouse models of graft-versus-host disease and experimental autoimmune encephalomyelitis. HGF-MET axis is also implicated in promoting thymopoiesis and the survival and migration of B lymphocytes. Recent studies have shown that MET signaling induces cardiotropism in activated T lymphocytes. Further understanding of the HGF-MET axis in the immune system would allow its therapeutic manipulation to improve immune cell reconstitution, restore immune homeostasis and to treat immuno-inflammatory diseases.
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PMID:The hepatocyte growth factor (HGF)-MET receptor tyrosine kinase signaling pathway: Diverse roles in modulating immune cell functions. 2682 8

Th17 cell differentiation and pathogenicity depend on metabolic reprogramming inducing shifts toward glycolysis. Here, we show that the pyruvate kinase M2 (PKM2), a glycolytic enzyme required for cancer cell proliferation and tumor progression, is a key factor mediating Th17 cell differentiation and autoimmune inflammation. We found that PKM2 is highly expressed throughout the differentiation of Th17 cells in vitro and during experimental autoimmune encephalomyelitis (EAE) development. Strikingly, PKM2 is not required for the metabolic reprogramming and proliferative capacity of Th17 cells. However, T cell-specific PKM2 deletion impairs Th17 cell differentiation and ameliorates symptoms of EAE by decreasing Th17 cell-mediated inflammation and demyelination. Mechanistically, PKM2 translocates into the nucleus and interacts with STAT3, enhancing its activation and thereby increasing Th17 cell differentiation. Thus, PKM2 acts as a critical nonmetabolic regulator that fine-tunes Th17 cell differentiation and function in autoimmune-mediated inflammation.
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PMID:PKM2 promotes Th17 cell differentiation and autoimmune inflammation by fine-tuning STAT3 activation. 3269 23