Crosstalk between Immune Cells and Adipocytes Requires Both Paracrine Factors and Cell Contact to Modify Cytokine Secretion: e77306
Increased adiposity results in a heightened infiltration of immune cells into fat depots, which in turn generates a pro-inflammatory phenotype in obese individuals. To better understand the causal factors that establish this pro-inflammatory profile, we examined events leading to crosstalk between a...
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Published in | PloS one Vol. 8; no. 10 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
01.10.2013
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Subjects | |
Online Access | Get full text |
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Summary: | Increased adiposity results in a heightened infiltration of immune cells into fat depots, which in turn generates a pro-inflammatory phenotype in obese individuals. To better understand the causal factors that establish this pro-inflammatory profile, we examined events leading to crosstalk between adipocytes and immune cells. Using isolated spleen-derived immune cells, stimulated with LPS, together with cultured adipocytes, we differentiated the effects of paracrine factors and cell-cell contact on TNF alpha , IL-6 and MCP-1 secretion levels and secretion profiles. When splenocytes and adipocytes were co-cultured without direct contact, permitting only paracrine communication, secretion of IL-6 and MCP-1 were increased by 3- and 2.5-fold, respectively, over what was secreted by individual cultures, whereas TNF alpha secretion was reduced by 55%. When cells were co-cultured with direct cell-cell contact, IL-6 and MCP-1 secretion were increased by an additional 36% and 38%, respectively, over that measured from just paracrine stimulation alone, indicating that cell contact provides a synergistic signal that amplifies elevated cytokine secretion stimulated by paracrine signals. Using splenocytes from TNF alpha -/- mice showed that the absence of TNF alpha has little effect on paracrine stimulation of cytokine secretion, but attenuates cell contact-mediated enhancement of IL-6 and MCP-1 secretion. Furthermore, TNF alpha supports cell contact-mediated signaling in part, but not exclusively, through Nuclear Factor- Kappa B activation. These findings indicate that engagement of cell contact between immune cells and adipocytes, in conjunction with locally secreted paracrine factors, activates a unique signaling pathway that mediates crosstalk between these cell types leading to marked effects on cytokine secretion and profile. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 content type line 23 ObjectType-Feature-1 |
ISSN: | 1932-6203 |
DOI: | 10.1371/journal.pone.0077306 |