T cell derived ghrelin is required for regulation of NFκB and T-helper 1 cytokines

T cell derived ghrelin is required for regulation of NFκB and T-helper 1 cytokines

e14 Abstracts / Brain, Behavior, and Immunity 20 (2006) e1–e16 cytokines produced by these DC precursors, i.e., IL-12 and IFN-a in healthy humans du...

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e14

Abstracts / Brain, Behavior, and Immunity 20 (2006) e1–e16

cytokines produced by these DC precursors, i.e., IL-12 and IFN-a in healthy humans during a regular sleep-wake cycle and during a 24-h period of continuous wakefulness. Blood was sampled every 1.5 h during night-time and every 3 h during daytime. Sleep strongly decreased the absolute count of CD14dimCD16+ monocytes, while the major CD14+CD16 monocyte population remained unaffected. Pre-mDC and PDC counts revealed a circadian rhythm but were not influenced by sleep. Compared with sustained wakefulness, nocturnal sleep strongly increased the number of IL-12 producing pre-mDC throughout the night, whereas IFN-a production showed only a circadian rhythm with peak time during late night and early morning, in paralleled with the peak of PDC blood numbers. Correlation analyses identified hormones (noradrenalin, cortisol, prolactin) as factors modulating APC counts and function during sleep. The profound influence of sleep on APC provides evidence that sleep beyond circadian rhythms critically contribute to the regulation of the adaptive immune processes. doi:10.1016/j.bbi.2006.04.026

non-silencing control sequence. Human T cells with down regulated endogenous ghrelin exhibited increased phosphorylated IjB compared to the control siRNA transfected cells, while ghrelin treatment of control T cells led to reduced phosphorylated IjB activity. Moreover, human immune cells also express GH mRNA upon T cell activation. However, compared to control siRNA transfected cells, the downregulation of endogenous GH in human T cell by RNA interference had little to no effect on ability of ghrelin to reduce IjB phosphorylation, suggesting that ghrelin’s effects on NFjB are mediated by a GH-independent mechanism. Activation of T cells transfected with ghrelin siRNA demonstrated significantly higher levels of the Th1-specific cytokines, IFN-c, IL-2, and TNF-a without affecting GM-CSF levels compared to control cells. These studies demonstrate, for the first time that T cell-derived ghrelin plays a critical role in regulating NFjB activity and Th1 cytokine production. Thus, the presence of ghrelin within immune microenvironment might serve an important homeostatic role in controlling the polarization of T cells to the more inflammatory Th1 phenotype in response to various physiological and pathological stimuli. Acknowledgment

T cell derived ghrelin is required for regulation of NFjB and T-helper 1 cytokines Vishwa D. Dixit, Anthony Cooper-Jenkins, Dennis D. Taub

This research was supported by the Intramural Research Program of the National Institute on Aging, NIH. doi:10.1016/j.bbi.2006.04.027

National Institute on Aging, NIH, USA Originally thought of as a stomach-derived endocrine peptide acting via its receptors in the CNS to stimulate food intake and GH expression, ghrelin and its receptor, GHS-R, are widely expressed in a number of organs, including the immune system. Our laboratory has recently demonstrated that ghrelin functions as a key signal coupling metabolic status to immune function and also inhibits proinflammatory cytokine expression by human T cells and accessory cells. Besides cytokines and various growth factors, immune cells also express hormones including GH and ghrelin; however, the biological relevance of ghrelin expression by human lymphocytes remains to be defined. In the current study, we have examined the impact of knocking down endogenous ghrelin expression by RNA interference on human T cell responses. Mononuclear cells derived from 5 healthy human donors were utilized for isolation of T cells, subsequently transfected with control, ghrelin and GH-specific siRNA constructs using electroporation and cultured for various time points on plate bound anti-CD3 antibody coated plates. Our results demonstrate that ghrelin mRNA is expressed in human T cells and that the active ghrelin protein (acylated ghrelin) is polarly expressed in the stimulated T cells. Utilizing a pool of four siRNA constructs specifically directed against ghrelin, we could achieve 40–65% knockdown of the endogenous ghrelin protein expression compared to a

Relations between depressive symptoms and cervical dysplasia in HIV+ women with human papillomavirus (HPV) infection Stacy M. Dodd a, Deidre Pereira a, Ilona Buscher b, Michele Peake b, Rachel Rose b, Trudi Simon b, Michael H. Antoni b, Mary Ann Fletcher b, Kevin Maher b a b

University of Florida, FL, USA University of Miami, FL, USA

Immunosuppressed HIV+ women with poorly controlled HIV viral load are at risk for human papillomavirus (HPV) induced cervical dysplasia, the asymptomatic precursor to cervical cancer. We previously reported high life stress increases odds of progressive/persistent cervical squamous intraepithelial lesions (SIL) in HIV+HPV+ women, possibly via effects on cellular immunity or health behaviors. No research has examined the relationship between stress-related mood impairment and cervical dysplasia risk in HIV+HPV+ women. This is important because depression, a highly prevalent condition among HIV+ women, is a significant predictor of poorer health care behaviors, neuroendocrine and immune dysregulation, and HIV disease progression. The present study examined the cross-sectional relationship between depressive symptoms and odds of cervical dysplasia among 55 primarily