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Brain Inflammation and Endoplasmic Reticulum Stress

  • Isin Cakir
  • Eduardo A. Nillni
Chapter

Abstract

In his medical treatise De Medicina dating back two millenniums, Aulus Cornelius Celsus refers to the signs of inflammation as “redness and swelling with heat and pain.” Inflammation is a reaction of the body to foreign stimuli and has presumably evolved to restore homeostasis in response to infections, tissue damage, or toxins. In conditions when the basal homeostatic state cannot be restored, persistent inflammatory signals usually lead to a maladaptive state as we observe in diet-induced obesity. Inflammatory process typically involves an inducing factor, such as bacterial infection, which is recognized by sensory molecules, e.g., as toll-like receptors, which then leads to secretion of inflammatory mediators including cytokines, chemokines, and a subclass of eicosanoids called prostaglandins. Final stage of the acute inflammatory cycle involves a resolution stage aimed to return to the pre-inflammatory homeostatic boundaries (Serhan et al. 2007), and failure to do so might lead to chronic inflammation. As opposed to acute inflammatory response commonly observed, following tissue injury or bacterial or viral infections, metabolic syndrome, and obesity per se manifest in the form of a chronic low-grade inflammatory state also called para−/meta-inflammation (Medzhitov 2008; Hotamisligil 2017). The inducing factor(s) of this chronic low-grade inflammation is still not entirely clear; however common mediators are involved in the acute and chronic inflammation. In contrast to many other chronic inflammatory conditions where the response is localized to the site of action of the inducing factor (e.g., site of infection), obesity-associated inflammation is manifested at a systemic level incorporating the peripheral as well as central tissues. Low-grade chronic inflammation has been demonstrated in a variety of metabolic tissues, such as the white adipose (Xu et al. 2003), liver (Cai et al. 2005), skeletal muscle (8, 9), and pancreas (Ehses et al. 2008; Donath et al. 2010), and appears to play a causative role in metabolic dysregulations including insulin resistance during obesity. For example, treatment with an anti-inflammatory agent amlexanox, an inhibitor of the NF-κB kinases IKKε and TBK-1, reduces obesity in rodents and improves glucose homeostasis in mice (Reilly et al. 2013) and a subset of diabetics (Oral et al. 2017).

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Life Sciences Institute and Department of Molecular and Integrative PhysiologyUniversity of MichiganAnn ArborUSA
  2. 2.Emeritus Professor of Medicine, Molecular Biology, Cell Biology & Biochemistry, Department of Medicine, Molecular Biology, Cell Biology & BiochemistryThe Warren Alpert Medical School of Brown UniversityProvidenceUSA

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