Linked Life Data

19833726

Source:http://linkedlifedata.com/resource/pubmed/id/19833726

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
49
pubmed:dateCreated
2009-11-30
pubmed:abstractText
CCL2 and interleukin (IL)-6 are among the most prevalent cytokines in the tumor microenvironment, with expression generally correlating with tumor progression and metastasis. CCL2 and IL-6 induced expression of each other in CD11b(+) cells isolated from human peripheral blood. It was demonstrated that both cytokines induce up-regulation of the antiapoptotic proteins cFLIP(L) (cellular caspase-8 (FLICE)-like inhibitory protein), Bcl-2, and Bcl-X(L) and inhibit the cleavage of caspase-8 and subsequent activation of the caspase-cascade, thus protecting cells from apoptosis under serum deprivation stress. Furthermore, both cytokines induced hyperactivation of autophagy in these cells. Upon CCL2 or IL-6 stimulation, CD11b(+) cells demonstrated a significant increase in the mannose receptor (CD206) and the CD14(+)/CD206(+) double-positive cells, suggesting a polarization of macrophages toward the CD206(+) M2-type phenotype. Caspase-8 inhibitors mimicked the cytokine-induced up-regulation of autophagy and M2 polarization. Furthermore, E64D and leupeptin, which are able to function as inhibitors of autophagic degradation, reversed the effect of caspase-8 inhibitors in the M2-macrophage polarization, indicating a role of autophagy in this mechanism. Additionally, in patients with advanced castrate-resistant prostate cancer, metastatic lesions exhibited an increased CD14(+)/CD206(+) double-positive cell population compared with normal tissues. Altogether, these findings suggest a role for CCL2 and IL-6 in the survival of myeloid monocytes recruited to the tumor microenvironment and their differentiation toward tumor-promoting M2-type macrophages via inhibition of caspase-8 cleavage and enhanced autophagy.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD11b, http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD14, http://linkedlifedata.com/resource/pubmed/chemical/BCL2L1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/CCL2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Caspase 8, http://linkedlifedata.com/resource/pubmed/chemical/Caspases, http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL2, http://linkedlifedata.com/resource/pubmed/chemical/Cytokines, http://linkedlifedata.com/resource/pubmed/chemical/ITGAM protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6, http://linkedlifedata.com/resource/pubmed/chemical/Leucine, http://linkedlifedata.com/resource/pubmed/chemical/Leupeptins, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2, http://linkedlifedata.com/resource/pubmed/chemical/aloxistatin, http://linkedlifedata.com/resource/pubmed/chemical/bcl-X Protein, http://linkedlifedata.com/resource/pubmed/chemical/leupeptin
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
4
pubmed:volume
284
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
34342-54
pubmed:dateRevised
2011-3-3
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
CCL2 and interleukin-6 promote survival of human CD11b+ peripheral blood mononuclear cells and induce M2-type macrophage polarization.
pubmed:affiliation
Department of Urology, University of Michigan, Ann Arbor, Michigan 48109, USA. rocach@umich.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural