Social stress up-regulates inflammatory gene expression in the leukocyte transcriptome via β-adrenergic induction of myelopoiesis.
Title | Social stress up-regulates inflammatory gene expression in the leukocyte transcriptome via β-adrenergic induction of myelopoiesis. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Powell ND, Sloan EK, Bailey MT, Arevalo JMG, Miller GE, Chen E, Kobor MS, Reader BF, Sheridan JF, Cole SW |
Journal | Proc Natl Acad Sci U S A |
Volume | 110 |
Issue | 41 |
Pagination | 16574-9 |
Date Published | 2013 Oct 8 |
ISSN | 1091-6490 |
Keywords | Animals, Computational Biology, Flow Cytometry, Gene Expression Profiling, Gene Expression Regulation, Granulocyte-Macrophage Colony-Stimulating Factor, Humans, Male, Mice, Mice, Inbred C57BL, Monocytes, Myelopoiesis, Propranolol, Receptors, Adrenergic, beta, Social Environment, Socioeconomic Factors, Stress, Psychological, Sympathetic Nervous System, Transcription Factors, Transcriptome |
Abstract | Across a variety of adverse life circumstances, such as social isolation and low socioeconomic status, mammalian immune cells have been found to show a conserved transcriptional response to adversity (CTRA) involving increased expression of proinflammatory genes. The present study examines whether such effects might stem in part from the selective up-regulation of a subpopulation of immature proinflammatory monocytes (Ly-6c(high) in mice, CD16(-) in humans) within the circulating leukocyte pool. Transcriptome representation analyses showed relative expansion of the immature proinflammatory monocyte transcriptome in peripheral blood mononuclear cells from people subject to chronic social stress (low socioeconomic status) and mice subject to repeated social defeat. Cellular dissection of the mouse peripheral blood mononuclear cell transcriptome confirmed these results, and promoter-based bioinformatic analyses indicated increased activity of transcription factors involved in early myeloid lineage differentiation and proinflammatory effector function (PU.1, NF-κB, EGR1, MZF1, NRF2). Analysis of bone marrow hematopoiesis confirmed increased myelopoietic output of Ly-6c(high) monocytes and Ly-6c(intermediate) granulocytes in mice subject to repeated social defeat, and these effects were blocked by pharmacologic antagonists of β-adrenoreceptors and the myelopoietic growth factor GM-CSF. These results suggest that sympathetic nervous system-induced up-regulation of myelopoiesis mediates the proinflammatory component of the leukocyte CTRA dynamic and may contribute to the increased risk of inflammation-related disease associated with adverse social conditions. |
DOI | 10.1073/pnas.1310655110 |
Alternate Journal | Proc. Natl. Acad. Sci. U.S.A. |
PubMed ID | 24062448 |
PubMed Central ID | PMC3799381 |
Grant List | AG033590 / AG / NIA NIH HHS / United States AG107265 / AG / NIA NIH HHS / United States CA116778 / CA / NCI NIH HHS / United States DE014320 / DE / NIDCR NIH HHS / United States HD058502 / HD / NICHD NIH HHS / United States MH093473 / MH / NIMH NIH HHS / United States MH46801 / MH / NIMH NIH HHS / United States P01 AG018911 / AG / NIA NIH HHS / United States P30 AG017265 / AG / NIA NIH HHS / United States R01 AG034052 / AG / NIA NIH HHS / United States R01 MH093473 / MH / NIMH NIH HHS / United States R01 MH097243 / MH / NIMH NIH HHS / United States R37 AG033590 / AG / NIA NIH HHS / United States |