Interleukin 18 activates MAPKs and STAT3 but not NF-κB in hippocampal HT-22 cells

Alboni, Silvia; Montanari, Claudia; Benatti, Cristina; Sanchez‐Alavez, Manuel; Rigillo, Giovanna; Blom, Johanna Maria Catharina; Brunello, Nicoletta; Conti, Bruno; Pariante, Carmine M.; Tascedda, Fabio

doi:10.1016/j.bbi.2014.02.015

Cited by 39 publications

(31 citation statements)

References 76 publications

(95 reference statements)

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“…IL-18 signaling is also mediated by p38 mitogen-activated protein kinase (MAPK) Tomura et al, 1998;Zhou et al, 2013;Alboni et al, 2014) and its downstream effector activating transcription factor (ATF2) (Cao et al, 2004;Amin et al, 2007). ATF2 has anti-apoptotic effect in the developing liver through a negative feedback involving the transcriptional activation of p38 kinase (Breitwieser et al, 2007).…”

Section: Discussionmentioning

confidence: 98%

Interleukin 18 augments growth ability via NF-κB and p38/ATF2 pathways by targeting cyclin B1, cyclin B2, cyclin A2, and Bcl-2 in BRL-3A rat liver cells

Zhang

Pan

et al. 2015

Gene

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Section: Discussionmentioning

confidence: 98%

Interleukin 18 augments growth ability via NF-κB and p38/ATF2 pathways by targeting cyclin B1, cyclin B2, cyclin A2, and Bcl-2 in BRL-3A rat liver cells

Zhang

Pan

et al. 2015

Gene

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“…IL-18 is involved in regulation of gene expression in the hippocampus (Alboni et al, 2014). It has been suggested that down-regulation of IL-18 is associated with peripheral adaptations related to the development of MetS (de Wit et al, 2008; Nyima et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Chronic psychological stress and high-fat high-fructose diet disrupt metabolic and inflammatory gene networks in the brain, liver, and gut and promote behavioral deficits in mice

Rodrigues

Bekhbat

Houser

et al. 2017

Brain, Behavior, and Immunity

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The mechanisms underlying the association between chronic psychological stress, development of metabolic syndrome (MetS), and behavioral impairment in obesity are poorly understood. The aim of the present study was to assess the effects of mild chronic psychological stress on metabolic, inflammatory, and behavioral profiles in a mouse model of diet-induced obesity. We hypothesized that (1) high-fat high-fructose diet (HFHF) and psychological stress would synergize to mediate the impact of inflammation on the central nervous system in the presence of behavioral dysfunction, and that (2) HFHF and stress interactions would impact insulin and lipid metabolism. C57Bl/6 male mice underwent a combination of HFHF and two weeks of chronic psychological stress. MetS-related conditions were assessed using untargeted plasma metabolomics, and structural and immune changes in the gut and liver were evaluated. Inflammation was measured in plasma, liver, gut, and brain. Our results show a complex interplay of diet and stress on gut alterations, energetic homeostasis, lipid metabolism, and plasma insulin levels. Psychological stress and HFHF diet promoted changes in intestinal tight junctions proteins and increases in insulin resistance and plasma cholesterol, and impacted the RNA expression of inflammatory factors in the hippocampus. Stress promoted an adaptive anti-inflammatory profile in the hippocampus that was abolished by diet treatment. HFHF increased hippocampal and hepatic Lcn2 mRNA expression as well as LCN2 plasma levels. Behavioral changes were associated with HFHF and stress. Collectively, these results suggest that diet and stress as pervasive factors exacerbate MetS-related conditions through an inflammatory mechanism that ultimately can impact behavior. This rodent model may prove useful for identification of possible biomarkers and therapeutic targets to treat metabolic syndrome and mood disorders.

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“…22 In addition to NF-kB, the IL-18/IL-18Rα/IL-18Rβ complex has been shown to induce phosphorylation of STAT3 in an NK and hippocampal cell lines and the p38 MAP kinase pathway in neutrophils. [23][24][25]…”

Section: Il-18receptorandsignalingpathwaysmentioning

confidence: 99%

Interleukin‐18: Biological properties and role in disease pathogenesis

Kaplanski

2017

Immunological Reviews

407

385

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Initially described as an interferon (IFN)γ-inducing factor, interleukin (IL)-18 is indeed involved in Th1 and NK cell activation, but also in Th2, IL-17-producing γδ T cells and macrophage activation. IL-18, a member of the IL-1 family, is similar to IL-1β for being processed by caspase 1 to an 18 kDa-biologically active mature form. IL-18 binds to its specific receptor (IL-18Rα, also known as IL-1R7) forming a low affinity ligand chain. This is followed by recruitment of the IL-18Rβ chain. IL-18 then uses the same signaling pathway as IL-1 to activate NF-kB and induce inflammatory mediators such as adhesion molecules, chemokines and Fas ligand. IL-18 also binds to the circulating high affinity IL-18 binding protein (BP), such as only unbound free IL-18 is active. IL-18Rα may also bind IL-37, another member of the IL-1 family, but in association with the negative signaling chain termed IL-1R8, which transduces an anti-inflammatory signal. IL-18BP also binds IL-37 and this acts as a sink for the anti-inflammatory properties of IL-37. There is now ample evidence for a role of IL-18 in various infectious, metabolic or inflammatory diseases such as influenza virus infection, atheroma, myocardial infarction, chronic obstructive pulmonary disease, or Crohn's disease. However, IL-18 plays a very specific role in the pathogenesis of hemophagocytic syndromes (HS) also termed Macrophage Activation Syndrome. In children affected by NLRC4 gain-of-function mutations, IL-18 circulates in the range of tens of nanograms/mL. HS is treated with the IL-1 Receptor antagonist (anakinra) but also specifically with IL-18BP. Systemic juvenile idiopathic arthritis or adult-onset Still's disease are also characterized by high serum IL-18 concentrations and are treated by IL-18BP.

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Interleukin 18 activates MAPKs and STAT3 but not NF-κB in hippocampal HT-22 cells

Cited by 39 publications

References 76 publications

Interleukin 18 augments growth ability via NF-κB and p38/ATF2 pathways by targeting cyclin B1, cyclin B2, cyclin A2, and Bcl-2 in BRL-3A rat liver cells

Interleukin 18 augments growth ability via NF-κB and p38/ATF2 pathways by targeting cyclin B1, cyclin B2, cyclin A2, and Bcl-2 in BRL-3A rat liver cells

Chronic psychological stress and high-fat high-fructose diet disrupt metabolic and inflammatory gene networks in the brain, liver, and gut and promote behavioral deficits in mice

Interleukin‐18: Biological properties and role in disease pathogenesis

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