The IL-33-induced p38-/JNK1/2-TNFα axis is antagonized by activation of β-adrenergic-receptors in dendritic cells

Helbig, Christiane; Weber, Florian; Andreas, Nico; Herdegen, Thomas; Gaestel, Matthias; Kamradt, Thomas; Drube, Sebastian

doi:10.1038/s41598-020-65072-3

Cited by 9 publications

(6 citation statements)

References 44 publications

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“…IRAK activates the classic MAPK-signaling pathway via tumor necrosis factor receptor associated factor 6 (TRAF6), leading, via MKK3 and MKK6 to activation of the p38 MAPK -MK2 signaling axis ( Dunne and O’Neill, 2003 ; Figure 1B ). Evidence for MK2 phosphorylation following activation of receptors in the IL-1R family includes in responses to IL-1β ( Raingeaud et al, 1995 ; Dunne and O’Neill, 2003 ), IL-33 ( Helbig et al, 2020 ; Petrova et al, 2020 ), and IL-18 ( Dunne and O’Neill, 2003 ).…”

Section: Activation Of P38 Mapk -Mk2 Signaling Aximentioning

confidence: 99%

The p38MAPK-MK2 Signaling Axis as a Critical Link Between Inflammation and Synaptic Transmission

Beamer

Corrêa

2021

Front. Cell Dev. Biol.

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p38 is a mitogen-activated protein kinase (MAPK), that responds primarily to stress stimuli. p38 has a number of targets for phosphorylation, including MAPK-activated protein kinase 2 (MK2). MK2 primarily functions as a master regulator of RNA-binding proteins, indirectly controlling gene expression at the level of translation. The role of MK2 in regulating the synthesis of pro-inflammatory cytokines downstream of inflammation and cellular stress is well-described. A significant amount of evidence, however, now points to a role for the p38MAPK-MK2 signaling axis in mediating synaptic plasticity through control of AMPA receptor trafficking and the morphology of dendritic spines. These processes are mediated through control of cytoskeletal dynamics via the activation of cofilin-1 and possibly control of the expression of Arc/Arg3.1. There is evidence that MK2 is necessary for group I metabotropic glutamate receptors long-term depression (mGluR-LTD). Disruption of this signaling may play an important role in mediating cognitive dysfunction in neurological disorders such as fragile X syndrome and Alzheimer’s disease. To date, the role of neuronal MK2 mediating synaptic plasticity in response to inflammatory stimuli has not yet been investigated. In immune cells, it is clear that MK2 is phosphorylated following activation of a broad range of cell surface receptors for cytokines and other inflammatory mediators. We propose that neuronal MK2 may be an important player in the link between inflammatory states and dysregulation of synaptic plasticity underlying cognitive functions. Finally, we discuss the potential of the p38MAPK-MK2 signaling axis as target for therapeutic intervention in a number of neurological disorders.

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Section: Activation Of P38 Mapk -Mk2 Signaling Aximentioning

confidence: 99%

The p38MAPK-MK2 Signaling Axis as a Critical Link Between Inflammation and Synaptic Transmission

Beamer

Corrêa

2021

Front. Cell Dev. Biol.

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“…Heart tissue regeneration is primarily promoted by anti-inflammatory cytokines (20,21). However, as TNF-α inhibits the function of adrenergic B receptors, it can disable these receptors to respond to sympathetic stimuli and inhibits cardiac responses through alterations in vascular mechanical demand (22). Reduced B-adrenergic receptor response can lead to a feedback increase in sympathetic hormones, which in turn results in a feedforward increase in pro-inflammatory cytokine TNF-α, leading to a self-perpetuating cycle that is now independent of pro-and anti-inflammatory response (20,21,23).…”

Section: Discussionmentioning

confidence: 99%

The effect of moderate-intensity aerobic training on serum levels of TNF-α and IL-6 in rats undergoing radiotherapy

Khaleghi

Salamat

Parastesh

et al. 2021

J Shahrekord Univ Med Sci

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Background and aims: One of the main potential problems of radiotherapy (RT) in breast cancer is the increase in treatment-related inflammation. This study aimed to investigate the effect of eight weeks of moderate-intensity aerobic training (AT) on serum levels of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in rats undergoing RT. Materials and Methods: In this experimental study, 32 male rats were randomly divided into four groups of eight members including (1) healthy control (C), (2) AT, (3) RT, and (4) AT + RT groups. Rats were first anesthetized with ketamine-xylazine solution (K, 60-90 kg/mg; Z, 6-10 kg/mg) and then located on a Plexiglas plate with a thickness of 1 cm. Photon beam RT was performed using X-rays with a dose of 11 Gy from an Elekta compact linear accelerator (Elekta Compact 6-MV China). AT program was performed for eight weeks, five days a week, and one session a day for 60 minutes (70-75% of VO2max). Afterwards, one-way ANOVA was run to examine the research variables. Results: According to the results, TNF-α was significantly higher in the RT group compared to the C group (P=0.003), whereas IL-6 levels were significantly lower in the AT + RT group compared to the RT group (P=0.001) and the C group (P=0.027). Further, the levels of this cytokine were significantly lower in the AT group compared to the RT group (P=0.006) and similarly in the RT group compared to the C group (P=0.03). Conclusion: RT led to an increase in pro-inflammatory cytokines; however, performing AT could only significantly reduce the IL-6 levels.

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“…TNF-a is upregulated in DC by interaction with antigens and by stimulation of TLRs, and it is a major inducer of T-cell responses (88)(89)(90). We also considered the expression of the beta-2 adrenergic receptor, a marker associated with tolerogenic DC (91)(92)(93), under the hypothesis that expression of beta-2 adrenergic receptor and TNF-a should be inversely correlated. Fluorescence single mRNA in-situ hybridization was performed on spleen sections for ADRB2 and TNF-a (Figure 7A).…”

Section: Tbi Strongly Induces the Immunogenic Function Of Splenic Dcsmentioning

confidence: 99%

Fast Maturation of Splenic Dendritic Cells Upon TBI Is Associated With FLT3/FLT3L Signaling

Zhang

Chandrasekar

et al. 2022

Front. Immunol.

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The consequences of systemic inflammation are a significant burden after traumatic brain injury (TBI), with almost all organs affected. This response consists of inflammation and concurrent immunosuppression after injury. One of the main immune regulatory organs, the spleen, is highly interactive with the brain. Along this brain–spleen axis, both nerve fibers as well as brain-derived circulating mediators have been shown to interact directly with splenic immune cells. One of the most significant comorbidities in TBI is acute ethanol intoxication (EI), with almost 40% of patients showing a positive blood alcohol level (BAL) upon injury. EI by itself has been shown to reduce proinflammatory mediators dose-dependently and enhance anti-inflammatory mediators in the spleen. However, how the splenic immune modulatory effect reacts to EI in TBI remains unclear. Therefore, we investigated early splenic immune responses after TBI with and without EI, using gene expression screening of cytokines and chemokines and fluorescence staining of thin spleen sections to investigate cellular mechanisms in immune cells. We found a strong FLT3/FLT3L induction 3 h after TBI, which was enhanced by EI. The FLT3L induction resulted in phosphorylation of FLT3 in CD11c+ dendritic cells, which enhanced protein synthesis, maturation process, and the immunity of dendritic cells, shown by pS6, peIF2A, MHC-II, LAMP1, and CD68 by immunostaining and TNF-α expression by in-situ hybridization. In conclusion, these data indicate that TBI induces a fast maturation and immunity of dendritic cells which is associated with FLT3/FLT3L signaling and which is enhanced by EI prior to TBI.

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The IL-33-induced p38-/JNK1/2-TNFα axis is antagonized by activation of β-adrenergic-receptors in dendritic cells

Cited by 9 publications

References 44 publications

The p38MAPK-MK2 Signaling Axis as a Critical Link Between Inflammation and Synaptic Transmission

The p38MAPK-MK2 Signaling Axis as a Critical Link Between Inflammation and Synaptic Transmission

The effect of moderate-intensity aerobic training on serum levels of TNF-α and IL-6 in rats undergoing radiotherapy

Fast Maturation of Splenic Dendritic Cells Upon TBI Is Associated With FLT3/FLT3L Signaling

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