title: Macrophage-associated mesenchymal stem cells assume an activated, migratory, pro-inflammatory phenotype with increased IL-6 and CXCL10 secretion.
abstract: Mesenchymal stem cells (MSCs) exhibit tropism for sites of tissue injury and tumors. However, the influence of the microenvironment on MSC phenotype and localization remains incompletely characterized. In this study, we begin to define a macrophage-induced MSC phenotype. These MSCs secrete interleukin-6 (IL-6), CCL5, and interferon gamma-induced protein-10 (CXCL10) and exhibit increased mobility in response to multiple soluble factors produced by macrophages including IL-8, CCL2, and CCL5. The pro-migratory phenotype is dependent on activation of a c-Jun N-terminal kinase (JNK) pathway. This work begins to identify the influence of macrophages on MSC biology. These interactions are likely to play an important role in the tissue inflammatory response and may provide insight into the migratory potential of MSCs in inflammation and tissue injury.
authors.affiliation: Department of Pharmacology, The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick, New Jersey, United States of America.
authors.forename: Kevin
authors.initials: K
authors.lastname: Anton
authors.forename: Debabrata
authors.initials: D
authors.lastname: Banerjee
authors.forename: John
authors.initials: J
authors.lastname: Glod
mesh_terms: D002465:Cell Movement; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000378:metabolism; D018946:Chemokine CCL5 / Q000096:biosynthesis / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000096:biosynthesis / Q000378:metabolism*; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism*; D016209:Interleukin-8 / Q000096:biosynthesis / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C111835:CCL2 protein, human; C483024:CCL5 protein, human; C114753:CXCL10 protein, human; C508606:CXCL8 protein, human; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D017077:Culture Media, Conditioned; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D048670:MAP Kinase Kinase 4