Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The amyloidogenic peptides, amyloid-beta (A beta) and human amylin, are the major constituents of amyloid deposits found in patients with the chronic degenerative disorders Alzheimer's disease (AD) and type 2 diabetes, respectively. Recent studies have shown that a variety of inflammatory proteins such as cytokines are associated with the amyloid deposits of AD brain tissues. Therefore, in the present study, we sought to determine whether A beta and/or human amylin could modulate the various inflammatory activities of eosinophils. We observed that human amylin but not A beta peptides inhibited the in vitro interleukin-5 (IL-5)-mediated survival of cord blood-derived eosinophils (CBEs) in a concentration-dependent manner. By contrast, rat amylin, a nonamyloidogenic peptide that is highly homologous to human amylin, failed to affect the IL-5-mediated survival of CBEs. Similar inhibitory effects of human amylin were observed for peripheral blood eosinophils. Human amylin also enhanced the release of the cytokine granulocyte-macrophage colony-stimulating factor by CBEs that were stimulated with the calcium ionophore A23187 but was incapable of directly stimulating CBEs to release cytokines. In addition, the A23187-induced release of the inflammatory lipid mediator leukotriene C4 by CBEs was augmented by human amylin. These results suggest that the amyloidogenic peptide human amylin is capable of amplifying the various inflammatory activities of eosinophils.
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PMID:The amyloidogenic peptide human amylin augments the inflammatory activities of eosinophils. 759 53

It has been shown that both calcitonin gene-related peptide (CGRP) and amylin bind weakly to calcitonin (CT) receptors in osteoclast-like cells formed in vitro and inhibit bone resorption by a cAMP-dependent mechanism. Osteoclasts are thought to be derived from cells of the monocyte macrophage lineage, in which CGRP, but not CT, induces cAMP production. In this study, we determined the presence of functional receptors for CGRP in mouse alveolar macrophages and the effects of this peptide on proliferation and osteoclastic differentiation in mouse alveolar and bone marrow-derived macrophages. Human CT did not stimulate cAMP production in macrophages. Human CGRP stimulated cAMP production in mouse alveolar macrophages and bone marrow-derived macrophages dose-dependently. Human amylin, which has 43% homology with human CGRP, also stimulated these macrophages to produce cAMP, but only at a 100-fold higher concentration. The increment in cAMP production induced by human CGRP and amylin was abolished by the addition of human CGRP(8-37), a selective antagonist for CGRP receptors. Specific binding of [125I]human CGRP to alveolar macrophages was detected (dissociation constant, 2.5 x 10(-8) M; binding sites, 1.4 x 10(4)/cell). Amylin, but not CT, displaced the bound [125I]human CGRP from alveolar macrophages, but at a 100-fold higher concentration. No specific binding of [125I]human CT and [125I]human amylin to alveolar macrophages could be detected. Pretreatment with human CGRP for 24 h dose-dependently suppressed DNA synthesis in alveolar macrophages induced by granulocyte-macrophage colony-stimulating factor (GM-CSF). CGRP also suppressed the number of macrophage colonies formed from bone marrow cells induced by macrophage colony-stimulating factor (M-CSF).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of calcitonin gene-related peptide (CGRP) in macrophages: the presence of functional receptors and effects on proliferation and differentiation into osteoclast-like cells. 819 34