Role of CARD9 in inflammatory signal pathway of peritoneal macrophages in severe acute pancreatitis

Wang, Jing; Tian, Jing; He, Yang‐huan; Yang, Zhiwen; Wang, Lin; Lai, Yuexing; Xu, Ping

doi:10.1111/jcmm.15559

Cited by 10 publications

(12 citation statements)

References 28 publications

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“…It has been studied that SYK can active Card9-NF-κB signaling and activating PAD4-NETs signaling through SYK-dependent reactive oxygen species production ( 25 , 31 ). NF-κB plays a crucial role in transcriptional activation of many proinflammatory genes, including the genes of cytokines and chemokines ( 25 , 49 , 50 ). NETs itself could cause inflammation, as well as through promoting a proinflammatory subtype transition of microglia or macrophage ( 17 , 19 , 51 , 52 ).…”

Section: Discussionmentioning

confidence: 99%

TREM1 Regulates Neuroinflammatory Injury by Modulate Proinflammatory Subtype Transition of Microglia and Formation of Neutrophil Extracellular Traps via Interaction With SYK in Experimental Subarachnoid Hemorrhage

Zeng

et al. 2021

Front. Immunol.

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Neuroinflammation is a key process in the pathogenesis of subarachnoid hemorrhage (SAH) and contributes to poor outcome in patients. The purpose of this study is to explore the effect of triggering receptor expressed on myeloid cells 1 (TREM1) in the SAH, as well as its potential mechanism. In our study, plasma levels of soluble TREM1 was increased significantly after SAH and correlated to SAH severity and serum C-reactiveprotein. TREM1 inhibitory peptide LP17 alleviated the neurological deficits, attenuated brain water content, and reduced neuronal damage after SAH. Meanwhile, TREM1 inhibitory peptide decreased neuroinflammation (evidenced by the decreased levels of markers including IL-6, IL-1β, TNF-α) by attenuating proinflammatory subtype transition of microglia (evidenced by the decreased levels of markers including CD68, CD16, CD86) and decreasing the formation of neutrophil extracellular traps (evidenced by the decreased levels of markers including CitH3, MPO, and NE). Further mechanistic study identified that TREM1 can activate downstream proinflammatory pathways through interacting with spleen tyrosine kinase (SYK). In conclusion, inhibition of TREM1 alleviates neuroinflammation by attenuating proinflammatory subtype transition of microglia and decreasing the formation of neutrophil extracellular traps through interacting with SYK after SAH. TREM1 may be a a promising therapeutic target for SAH.

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Section: Discussionmentioning

confidence: 99%

TREM1 Regulates Neuroinflammatory Injury by Modulate Proinflammatory Subtype Transition of Microglia and Formation of Neutrophil Extracellular Traps via Interaction With SYK in Experimental Subarachnoid Hemorrhage

Zeng

et al. 2021

Front. Immunol.

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“…MyD88 activation and CARD9-mediated IFN-γ production are critically involved in preventing the infection of coccidioides in mice ( 61 ). Deletion of CARD9 with siRNA inhibits the signaling from TLR4 and Dectin‐1 in macrophages and reduces the phosphorylation of NF‐κB and p38 MAPKs, leading to decreased production of inflammatory cytokines ( 62 ).…”

Section: Card9 Signaling Is Critical For the Production Of Cytokines/...mentioning

confidence: 99%

CARD9 Signaling, Inflammation, and Diseases

et al. 2022

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Caspase-recruitment domain 9 (CARD9) protein is expressed in many cells especially in immune cells, and is critically involved in the function of the innate and adaptive immune systems through extensive interactions between CARD9 and other signaling molecules including NF-κB and MAPK. CARD9-mediated signaling plays a central role in regulating inflammatory responses and oxidative stress through the productions of important cytokines and chemokines. Abnormalities of CARD9 and CARD9 signaling or CARD9 mutations or polymorphism are associated with a variety of pathological conditions including infections, inflammation, and autoimmune disorders. This review focuses on the function of CARD9 and CARD9-mediated signaling pathways, as well as interactions with other important signaling molecules in different cell types and the relations to specific disease conditions including inflammatory diseases, infections, tumorigenesis, and cardiovascular pathologies.

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“…For example, studies have shown that signaling complexes, comprising of CARD9-BCL10-Malt 1, play critical roles in the activation of NF-κB signaling pathway in C-type lectin receptor (CLR) induced inflammatory responses [ 46 ]. Published evidence also suggests strong connection between over expression of CARD9 in the activation of p38 MAPK during inflammation [ 47 , 48 ]. Lastly, studies by Wang and coworkers have demonstrated that obesity promotes activation of p38MAPK through the upregulation of CARD9-BCL10 complex [ 49 ].…”

Section: Resultsmentioning

confidence: 99%

CARD9 Mediates Pancreatic Islet Beta-Cell Dysfunction Under the Duress of Hyperglycemic Stress

Gamage

Hali

Chen

et al. 2022

Cell Physiol Biochem

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BACKGROUND/AIMS: Published evidence implicates Caspase recruitment domain containing protein 9 (CARD9) in innate immunity. Given its recently suggested roles in obesity and insulin resistance, we investigated its regulatory role(s) in the onset of islet beta cell dysfunction under chronic hyperglycemic (metabolic stress) conditions. METHODS: Islets from mouse pancreas were isolated by the collagenase digestion method. Expression of CARD9 was suppressed in INS-1 832/13 cells by siRNA transfection using the DharmaFect1 reagent. The degree of activation of Rac1 was assessed by a pull-down assay kit. Interactions between CARD9, RhoGDIβ and Rac1 under metabolic stress conditions were determined by co-immunoprecipitation assay. The degree of phosphorylation of stress kinases was assessed using antibodies directed against phosphorylated forms of the respective kinases. RESULTS: CARD9 expression is significantly increased following exposure to high glucose, not to mannitol (both at 20 mM; 24 hrs.) in INS-1 832/13 cells. siRNA-mediated knockdown of CARD9 significantly attenuated high glucose-induced activation of Rac1 and phosphorylation of p38MAPK and p65 subunit of NF-κB (RelA), without significantly impacting high glucose-induced effects on JNK1/2 and ERK1/2 activities. CARD9 depletion also suppressed high glucose-induced CHOP expression (a marker for endoplasmic reticulum stress) in these cells. Co-immunoprecipitation studies revealed increased association between CARD9-RhoGDIβ and decreased association between RhoGDIβ-Rac1 in cells cultured under high glucose conditions. CONCLUSION: Based on these data, we conclude that CARD9 regulates activation of Rac1-p38MAPK-NFκB signaling pathway leading to functional abnormalities in beta cells under metabolic stress conditions.

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Role of CARD9 in inflammatory signal pathway of peritoneal macrophages in severe acute pancreatitis

Cited by 10 publications

References 28 publications

TREM1 Regulates Neuroinflammatory Injury by Modulate Proinflammatory Subtype Transition of Microglia and Formation of Neutrophil Extracellular Traps via Interaction With SYK in Experimental Subarachnoid Hemorrhage

TREM1 Regulates Neuroinflammatory Injury by Modulate Proinflammatory Subtype Transition of Microglia and Formation of Neutrophil Extracellular Traps via Interaction With SYK in Experimental Subarachnoid Hemorrhage

CARD9 Signaling, Inflammation, and Diseases

CARD9 Mediates Pancreatic Islet Beta-Cell Dysfunction Under the Duress of Hyperglycemic Stress

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