68. Relationships between global epigenetic modifications and NK cell function in women with breast cancer

A diagnosis of breast cancer results in psychosocial distress measured by increased perceived stress (PSS) and depressive mood (CES-D). This psychosocial distress is accompanied by reduced NK cell activity and elevated proinflammatory cytokine production (i.e., immune dysregulation). The effect of p...

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Bibliographic Details
Published inBrain, behavior, and immunity Vol. 26; p. S19
Main Authors Krukowski, K, Eddy, J.L, Tell, D, Janusek, L, Mathews, H.L
Format Journal Article
LanguageEnglish
Published Elsevier Inc 01.09.2012
Subjects
Allergy and Immunology
Psychiatry
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Summary:A diagnosis of breast cancer results in psychosocial distress measured by increased perceived stress (PSS) and depressive mood (CES-D). This psychosocial distress is accompanied by reduced NK cell activity and elevated proinflammatory cytokine production (i.e., immune dysregulation). The effect of psychosocial distress on immune dysregulation has been attributed to elevations in glucocorticoids, such as cortisol. Glucocorticoids can impact gene transcription and alter epigenetic modifications. The purpose of this study was to identify epigenetic modifications hypothesized to underlie this immune dysregulation during periods of psychosocial distress. Global epigenetic modifications were analyzed in woman diagnosed with breast cancer and a matched cancer free group. Relationships among psychosocial distress and global acetylation of histone 4-lysine −8 (H4-K8-Ac) and global phosphorylation of histone 3-serine 10 (H3-S10-P) were measured in NK cells. A significant negative correlation was measured between PSS and global H4-K8-Ac. In contrast, a positive significant correlation was observed among global H4-K8-Ac with NKCA and intracellular perforin levels. Further analysis found the effect of cortisol on perforin to be significantly mediated by global H4-K8-Ac. Conversely, a strong positive relationship was measured between PSS, H3-S10-P and with intracellular interferon gamma levels These data suggest global H4-H8-Ac and H3-S10-P to be important epigenetic modifications associated with both the immune suppressive and immune enhancing effects demonstrable in women experiencing this naturalistic stressor.
ISSN:0889-1591
1090-2139
DOI:10.1016/j.bbi.2012.07.092