Serum amyloid A induces interleukin-1β secretion from keratinocytes via the NACHT, LRR and PYD domains-containing protein 3 inflammasome

Yu, Na; Liu, Shuzhong; Xie, Yonggang; Zhang, S.; Ding, Yangfeng

doi:10.1111/cei.12458

Cited by 44 publications

(63 citation statements)

References 38 publications

(52 reference statements)

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“…Based on the Proteome Profiler ™ Array (R&D Systems, Minneapolis, MN, USA) results, we found that MSU selectively leads to the phosphorylation of two MAP kinase proteins: MAPK14/p38α and ERK1/2. This observation suggests that these two kinases are involved in the recognition of the MSU, and their activation leads to the upregulation of TLR2 , which occurs in several skin disorders for the recognition of microbial pathogens . This mechanism is similar to that reported for polycytidylic acid (Poly[I:C]), a TLR3 agonist that stimulates IL‐8/CXCL8 production in keratinocytes …”

Section: Discussionsupporting

confidence: 69%

The release of pro‐inflammatory cytokines is mediated via mitogen‐activated protein kinases rather than by the inflammasome signalling pathway in keratinocytes

Ondet

Muscatelli-Groux

Coulouarn

et al. 2017

Clin Exp Pharma Physio

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Toll-like receptors (TLRs) are expressed in the skin and airway epithelial tissues, which are the most important sites of host-pathogen interactions. TLRs recognize the 3-D structures of pathogen-associated molecules and are therefore useful markers of the innate immune response. Here, we investigated the role of lipopolysaccharides and monosodium urate (MSU) crystals in the activation of the TLR and NOD-like receptor (NLR) pathways in human keratinocytes. Analysis of the inflammasome compounds revealed that NOD-like receptor P3 and TLR4, both of which are components of inflammasome complexes involved in the activation of interleukin (IL)-1β, were not expressed in keratinocytes. Transcriptomic analysis showed that the combination of MSU and lipopolysaccharide priming did not elicit significant results compared to MSU treatment, which induced the expression of TLR2, IL-6 and IL-8/chemokine (C-X-C motif) ligand 8 CXCL8 in the keratinocyte cell line HaCaT. Furthermore, MSU promoted the phosphorylation of extracellular signal-regulated kinase 1/2 and MAPK14/p38α mitogen-activated protein kinases. We concluded that MSU stimulates a pro-inflammatory response in keratinocytes via mitogen-activated protein kinase pathway to induce production of IL-8/CXCL8 chemokine (C-X-C motif) ligand 8 and TLR2.

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Section: Discussionsupporting

confidence: 69%

The release of pro‐inflammatory cytokines is mediated via mitogen‐activated protein kinases rather than by the inflammasome signalling pathway in keratinocytes

Ondet

Muscatelli-Groux

Coulouarn

et al. 2017

Clin Exp Pharma Physio

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“…Although the function of SAA1 is well described for liver and immune cells, any role in muscle is less well understood. For example, SAA1 can bind to several receptors, such as TLR2, TLR4, CD36, P2RX7, VIMP, and SCARB1, which are expressed on hepatocytes, keratinocytes, fibroblasts, and macrophages . Whether or not these receptors are involved in SAA1 signalling in myocytes was uncertain.…”

Section: Discussionmentioning

confidence: 99%

Serum amyloid A1 mediates myotube atrophy via Toll‐like receptors

Hahn

Kny

Pablo‐Tortola

et al. 2019

J cachexia sarcopenia muscle

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Background Critically ill patients frequently develop muscle atrophy and weakness in the intensive‐care‐unit setting [intensive care unit‐acquired weakness (ICUAW)]. Sepsis, systemic inflammation, and acute‐phase response are major risk factors. We reported earlier that the acute‐phase protein serum amyloid A1 (SAA1) is increased and accumulates in muscle of ICUAW patients, but its relevance was unknown. Our objectives were to identify SAA1 receptors and their downstream signalling pathways in myocytes and skeletal muscle and to investigate the role of SAA1 in inflammation‐induced muscle atrophy. Methods We performed cell‐based in vitro and animal in vivo experiments. The atrophic effect of SAA1 on differentiated C2C12 myotubes was investigated by analysing gene expression, protein content, and the atrophy phenotype. We used the cecal ligation and puncture model to induce polymicrobial sepsis in wild type mice, which were treated with the IкB kinase inhibitor Bristol‐Myers Squibb (BMS)‐345541 or vehicle. Morphological and molecular analyses were used to investigate the phenotype of inflammation‐induced muscle atrophy and the effects of BMS‐345541 treatment. Results The SAA1 receptors Tlr2, Tlr4, Cd36, P2rx7, Vimp, and Scarb1 were all expressed in myocytes and skeletal muscle. Treatment of differentiated C2C12 myotubes with recombinant SAA1 caused myotube atrophy and increased interleukin 6 (Il6) gene expression. These effects were mediated by Toll‐like receptors (TLR) 2 and 4. SAA1 increased the phosphorylation and activity of the transcription factor nuclear factor ‘kappa‐light‐chain‐enhancer' of activated B‐cells (NF‐κB) p65 via TLR2 and TLR4 leading to an increased binding of NF‐κB to NF‐κB response elements in the promoter region of its target genes resulting in an increased expression of NF‐κB target genes. In polymicrobial sepsis, skeletal muscle mass, tissue morphology, gene expression, and protein content were associated with the atrophy response. Inhibition of NF‐κB signalling by BMS‐345541 increased survival (28.6% vs. 91.7%, P < 0.01). BMS‐345541 diminished inflammation‐induced atrophy as shown by a reduced weight loss of the gastrocnemius/plantaris (vehicle: −21.2% and BMS‐345541: −10.4%; P < 0.05), tibialis anterior (vehicle: −22.7% and BMS‐345541: −17.1%; P < 0.05) and soleus (vehicle: −21.1% and BMS‐345541: −11.3%; P < 0.05) in septic mice. Analysis of the fiber type specific myocyte cross‐sectional area showed that BMS‐345541 reduced inflammation‐induced atrophy of slow/type I and fast/type II myofibers compared with vehicle‐treated septic mice. BMS‐345541 reversed the inflammation‐induced atrophy program as indicated by a reduced expression of the atrogenes Trim63/MuRF1, Fbxo32/Atrogin1, and Fbxo30/MuSA1. Conclusions SAA1 activates the TLR2/TLR4//NF‐κB p65 signalling pathway to cause myocyte atrophy. Systemic inhibition of the NF‐κB pathway reduced muscle atrophy and increased survival of septic mice. The SAA1/TLR2/TLR4//NF‐κB p65 atrophy pathway could have utility in combatting ICUAW.

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“…Of note, the acute-phase response protein serum amyloid A1 (SAA1) was shown to be synthesized by and released from muscle of critically ill patients and septic mice [36]. SAA1 induces IL-1β expression [46] and secretion [47] and activates the Nlrp3 inflammasome in immune cells [46]. The Nlrp3 inflammasome is contained and active in C2C12 myocytes [48] .…”

Section: Discussionmentioning

confidence: 99%

Deletion of Nlrp3 protects from inflammation-induced skeletal muscle atrophy

Huang

Kny

Riediger

et al. 2017

ICMx

106

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BackgroundCritically ill patients develop atrophic muscle failure, which increases morbidity and mortality. Interleukin-1β (IL-1β) is activated early in sepsis. Whether IL-1β acts directly on muscle cells and whether its inhibition prevents atrophy is unknown. We aimed to investigate if IL-1β activation via the Nlrp3 inflammasome is involved in inflammation-induced atrophy.MethodsWe performed an experimental study and prospective animal trial. The effect of IL-1β on differentiated C2C12 muscle cells was investigated by analyzing gene-and-protein expression, and atrophy response. Polymicrobial sepsis was induced by cecum ligation and puncture surgery in Nlrp3 knockout and wild type mice. Skeletal muscle morphology, gene and protein expression, and atrophy markers were used to analyze the atrophy response. Immunostaining and reporter-gene assays showed that IL-1β signaling is contained and active in myocytes.ResultsImmunostaining and reporter gene assays showed that IL-1β signaling is contained and active in myocytes. IL-1β increased Il6 and atrogene gene expression resulting in myocyte atrophy. Nlrp3 knockout mice showed reduced IL-1β serum levels in sepsis. As determined by muscle morphology, organ weights, gene expression, and protein content, muscle atrophy was attenuated in septic Nlrp3 knockout mice, compared to septic wild-type mice 96 h after surgery.ConclusionsIL-1β directly acts on myocytes to cause atrophy in sepsis. Inhibition of IL-1β activation by targeting Nlrp3 could be useful to prevent inflammation-induced muscle failure in critically ill patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s40635-016-0115-0) contains supplementary material, which is available to authorized users.

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Serum amyloid A induces interleukin-1β secretion from keratinocytes via the NACHT, LRR and PYD domains-containing protein 3 inflammasome

Cited by 44 publications

References 38 publications

The release of pro‐inflammatory cytokines is mediated via mitogen‐activated protein kinases rather than by the inflammasome signalling pathway in keratinocytes

The release of pro‐inflammatory cytokines is mediated via mitogen‐activated protein kinases rather than by the inflammasome signalling pathway in keratinocytes

Serum amyloid A1 mediates myotube atrophy via Toll‐like receptors

Deletion of Nlrp3 protects from inflammation-induced skeletal muscle atrophy

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