Novel insights into the neuroendocrine control of inflammation: the role of GR and PARP1

Abstract

Inflammatory responses are elicited after injury, involving release of inflammatory mediators that ultimately lead, at the molecular level, to the activation of specific transcription factors (TFs; mainly activator protein 1 and nuclear factor-κB). These TFs propagate inflammation by inducing the expression of cytokines and chemokines. The neuroendocrine system has a determinant role in the maintenance of homeostasis, to avoid exacerbated inflammatory responses. Glucocorticoids (GCs) are the key neuroendocrine regulators of the inflammatory response. In this study, we describe the molecular mechanisms involved in the interplay between inflammatory cytokines, the neuroendocrine axis and GCs necessary for the control of inflammation. Targeting and modulation of the glucocorticoid receptor (GR) and its activity is a common therapeutic strategy to reduce pathological signaling. Poly (ADP-ribose) polymerase 1 (PARP1) is an enzyme that catalyzes the addition of PAR on target proteins, a post-translational modification termed PARylation. PARP1 has a central role in transcriptional regulation of inflammatory mediators, both in neuroendocrine tumors and in CNS cells. It is also involved in modulation of several nuclear receptors. Therefore, PARP1 and GR share common inflammatory pathways with antagonic roles in the control of inflammatory processes, which are crucial for the effective maintenance of homeostasis.

Identification of Proteins Associated with an IFNγ-Responsive Promoter by a Retroviral Expression System for enChIP Using CRISPR

“…In the list of proteins whose association with the IRF-1 promoter increased by IFNγ stimulation, we detected several classes of proteins: (i) proteins whose involvement in transcriptional regulation is suggested including DDX1 [29] , PARP1 [30] – [32] , CKAP4 [33] , Pescadillo homolog [34] , transcriptional activator protein PURβ [35] , activated RNA polymerase II transcriptional activator p15 (TCP4) [36] , [37] , BTF3 [38] , and Myb-binding protein 1A [39] , (ii) proteins involved in histone deacetylation and/or corepressor function including RBBP4 [40] , [41] , PA2G4 [42] , and TBL3 [43] , [44] , (iii) protein arginine N-methyltransferase 1 (PRMT1) [45] , [46] , (iv) DNA topoisomerase 2α [47] , and (v) histones including histone H2A.Z and histone H3.2.…”

Microemboli alter the acute stress response and cause prolonged expression of MCP-1 in the hippocampus

“…We hypothesized that because glucocorticoids are a potent anti-inflammatory, primarily mediated through Gr (Aprile-Garcia et al, 2014) and cytokine mediated pathways (Smoak and Cidlowski, 2004), exposure to CSDS after acute ischemic injury would be sufficient to disinhibit inflammatory gene expression in rats exposed to ME. Stress induced changes, particularly in the hippocampus, are well documented (Koo et al, 2010) and stress induced increases in inflammatory cytokines have been detected in response to chronic mild unpredictable stress (Koo et al, 2010) and social stress (Slavich and Irwin, 2014).…”

Contemporary Prevention Areas of Diabetes and Its Complications: The Role of the Family Physician

“…Острое воспаление является реакцией организма на инфекцию или повреждение тканей и требует как врожденного, так и адаптивного иммунного ответа. Воспаление состоит из провоспалительной фазы, фазы адаптации и фазы завершения [2,3]. Незавершенное, хроническое воспаление является основной причиной патогенеза таких заболеваний как диабет и онкология.…”

“…Незавершенное, хроническое воспаление является основной причиной патогенеза таких заболеваний как диабет и онкология. В воспалительном процессе участвуют тучные клетки, моноциты/макрофаги, эозинофилы, нейтрофилы, дендритные клетки (DC), Ви Т-лимфоциты [3,4]. Ключевым событием при воспалении является мобилизация нейтрофилов, миграция и активация которых направляется хемоаттрактантами.…”