Deficiency in cold-inducible RNA-binding protein attenuates acute respiratory distress syndrome induced by intestinal ischemia-reperfusion

Cen, Cindy; McGinn, Joseph T.; Aziz, Monowar; Yang, Weng Lang; Cagliani, Joaquín; Nicastro, Jeffrey; Coppa, Gene F.; Wang, Haichao

doi:10.1016/j.surg.2017.06.004

Cited by 32 publications

(26 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Multiple linear regression analysis indicated that the length of CPB time and IL-6 level contribute to CIRP production. However, Wang et al found that CIRP derived from macrophages induced IL-6 secretion, which exacerbated organ damage [13,16]. Based on these findings, we speculated that the length of CPB time is an important contributor to upregulation of CIRP.…”

Section: Discussionmentioning

confidence: 82%

“…Furthermore, CIRP plays important roles in tumor suppression or promotion [11,12] and has deleterious effects during hemorrhagic and septic shock [13]. Increased plasma CIRP is associated with poor prognosis of inflammatory-related diseases [14,15], and blockade of endogenous CIRP attenuates the multiple organ dysfunction [16,17]. It is well known that CIRP initiates a systemic inflammatory responses that leads to undesirable outcomes.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Plasma Cold-Inducible RNA-Binding Protein Predicts Lung Dysfunction After Cardiovascular Surgery Following Cardiopulmonary Bypass: A Prospective Observational Study

Xia

Jiang

et al. 2019

Med Sci Monit

View full text Add to dashboard Cite

Background Cold-inducible RNA-binding protein (CIRP) has been identified as an inflammatory mediator that exerts its function in inflammatory diseases. However, the roles of CIRP in patients who received cardiovascular surgery necessitating cardiopulmonary bypass (CPB) are still unknown. The aim of this study was to examine CIRP levels and attempt to evaluate whether CIRP could serve as a predictor for lung dysfunction after cardiovascular surgery. Material/Methods Plasma CIRP levels were detected by ELISA in 31 patients who received cardiovascular surgery at different time points. Selective inflammatory cytokines (TNF-α, IL-6, IL-10, and TLR4) and mediators (Ang II, PAI-1, and soluble E-selectin) were also detected. Selective laboratory and clinical parameters were recorded at scheduled time points. Results Compared with pre-operation levels, CIRP levels significantly increased 6 h after cardiovascular surgery with CPB. Multiple linear regression analysis showed that the length of CPB time contributed to CIRP production ( P =0.013). Furthermore, CIRP was associated with Ang II (r=0.438, P =0.016), PAI-1 (r=0.485, P =0.006), and soluble E-selectin (r=0.470, P =0.008), which partly reflected lung injuries. Multiple linear regression analysis showed that CIRP levels were independently associated with PaO 2 /FiO 2 ratios ( P =0.021). Conclusions The length of CPB time contributed to the upregulation of CIRP in patients who received cardiovascular surgery with CPB. CIRP levels could serve as a biomarker to predict the onset of lung injury induced by cardiovascular surgery.

show abstract

Section: Discussionmentioning

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Plasma Cold-Inducible RNA-Binding Protein Predicts Lung Dysfunction After Cardiovascular Surgery Following Cardiopulmonary Bypass: A Prospective Observational Study

Xia

Jiang

et al. 2019

Med Sci Monit

View full text Add to dashboard Cite

show abstract

“…CIRP is a novel DAMP causing exaggerated inflammation and injury to the lungs in murine sepsis as well as after direct administration of rmCIRP into the mice 4,10 . We previously showed that CIRP induces neutrophil infiltration, endothelial cell dysfunction by upregulating NLRP3 inflammasome and endoplasmic reticulum (ER) stress in lungs to cause ALI 8–10,25 . In the present study, we demonstrated that CIRP induced NET formation in the lungs during sepsis and following treatment of healthy mice with rmCIRP.…”

Section: Discussionmentioning

confidence: 99%

Cold-inducible RNA-binding Protein Induces Neutrophil Extracellular Traps in the Lungs during Sepsis

Ode

Aziz

Jin

et al. 2019

Sci Rep

Self Cite

View full text Add to dashboard Cite

Extracellular cold-inducible RNA-binding protein (CIRP) exaggerates inflammation and tissue injury in sepsis. Neutrophil extracellular traps (NETs) are released by activated neutrophils during sepsis. NETs contribute to pathogen clearance, but excessive NET formation (NETosis) causes inflammation and tissue damage. Peptidylarginine deiminase 4 (PAD4) is associated with NETosis by increasing histone citrullination and chromatin decondensation. We hypothesized that CIRP induces NETosis in the lungs during sepsis via upregulating PAD4 expression. Sepsis was induced in C57BL/6 wild-type (WT) and CIRP −/− mice by cecal ligation and puncture (CLP). After 20 h of CLP induction, NETs in the lungs of WT and CIRP −/− mice were quantified by flow cytometry by staining the single cell suspensions with MPO and CitH3 Abs. PAD4 expression in the lungs of WT and CIRP −/− mice after sepsis was assessed by Western blotting. In vitro effects of recombinant mouse (rm) CIRP for NETosis and PAD4 expression in the bone marrow-derived neutrophils (BMDN) were assessed by flow cytometry and Western blotting, respectively. After 20 h of CLP, NETosis in the lungs was significantly decreased in CIRP −/− mice compared to WT mice, which also correlated with the decreased PAD4 expression. Intratracheal administration of rmCIRP into WT mice significantly increased NETosis and PAD4 expression in the lungs compared to vehicle-injected mice. In vitro culture of BMDN with rmCIRP significantly increased NETosis and PAD4 expression compared to PBS-treated control. Fluorescence microscopy revealed typical web-like structures consistent with NETs in rmCIRP-treated BMDN. Thus, CIRP serves as a novel inducer of NETosis via PAD4 during sepsis.

show abstract

“…An in vitro study using macrophages showed that cellular necrosis does not cause CIRP release, thus suggesting that passive release is not a major source of eCIRP during hypoxia or endotoxemia . However, under in vivo condition like other DAMPs, passive release due to cell necrosis might play a role for eCIRP in injury such as I/R and sepsis . Future studies on the involvement of the inflammasome‐induced pore forming protein gasdermin D, various carrier/transport proteins, and the involvement of ER stress molecules for active release of CIRP during inflammation help understand how eCIRP gets secreted to the extracellular space.…”

Section: Mechanism: How Does Cirp's Expression Translocation and Sementioning

confidence: 99%

“…eCIRP's role as a key inflammatory mediator has been scrutinized in various inflammatory disease conditions. CIRP −/− mice subjected to models of HS, organ‐targeted ischemic/reperfusion injury and sepsis exhibit protective effects, such as the attenuated organ dysfunction and improved survival, suggesting eCIRP plays a critical role as in the development of inflammation and injury in these disease models . Indeed, administration of recombinant CIRP to healthy rats is sufficient to increase serum levels of TNF‐α, IL‐6, and high mobility group box‐1 (HMGB1), and induce liver injury, as assessed by increased levels of the organ injury markers aspartate aminotransferase (AST) and alanine aminotransferase (ALT) .…”

Section: Mechanism: How Does Extracellular Cirp Exaggerate Inflammation?mentioning

confidence: 99%

Extracellular CIRP (eCIRP) and inflammation

Aziz

Brenner

Wang

2019

Journal of Leukocyte Biology

Self Cite

158

188

View full text Add to dashboard Cite

Cold-inducible RNA-binding protein (CIRP) was discovered 2 decades ago while studying the mechanism of cold stress adaptation in mammals. Since then, the role of intracellular CIRP (iCIRP) as a stress-response protein has been extensively studied. Recently, extracellular CIRP (eCIRP) was discovered to also have an important role, acting as a damage-associated molecular pattern, raising critical implications for the pathobiology of inflammatory diseases. During hemorrhagic shock and sepsis, inflammation triggers the translocation of CIRP from the nucleus to the cytosol and its release to the extracellular space. eCIRP then induces inflammatory responses in macrophages, neutrophils, lymphocytes, and dendritic cells. eCIRP also induces endoplasmic reticulum stress and pyroptosis in endothelial cells by activating the NF-B and inflammasome pathways, and necroptosis in macrophages via mitochondrial DNA damage. eCIRP works through the TLR4-MD2 receptors. Studies with CIRP −/− mice reveal protection against inflammation, implicating eCIRP to be a novel drug target. Anti-CIRP Ab or CIRP-derived small peptide may have effective therapeutic potentials in sepsis, acute lung injury, and organ ischemia/reperfusion injuries. The current review focuses on the pathobiology of eCIRP by emphasizing on signal transduction machineries, leading to discovering novel therapeutic interventions targeting eCIRP in various inflammatory diseases. K E Y W O R D S ALI, CIRP, DAMP, eCIRP, hemorrhage, inflammation, ischemia/reperfusion, macrophage, neutrophils, sepsis PMN, polymorphonuclear neutrophils; RA, rheumatoid arthritis; RM, reverse migrated; rTEM, reverse transendothelial migration; STAT3, signal transducer and activator of transcription 3; TRPV, transient receptor potential vanilloid; UC, ulcerative colitis telomerase maintenance, 7 stress adaptation, 8 and tumor formation and progression. 9,10 These iCIRP activities, which allow cells to cope with various cellular stress conditions, have been reviewed in detail. 8 In contrast to iCIRP, extracellular CIRP (eCIRP) was recently discovered to act as a damage-associated molecular pattern (DAMP) promoting inflammation and injury. 11 The identification of eCIRP as a new DAMP has originated a new era of investigation in inflammation pathobiology. Serum levels of eCIRP not only were found to be elevated in individuals admitted to the intensive care unit (ICU)with hemorrhagic shock (HS), but also correlated with organ injury. 11 Furthermore, it was demonstrated that eCIRP was able to promote inflammation independently. 11 In cells subjected to hypoxia, CIRP translocates from its usual location in the nucleus to the cytosol 1,12 and is then released to the extracellular space. 11 eCIRP then acts as a DAMP increasing macrophage production of proinflammatory cytokines. 11 Since its original discovery as a DAMP, eCIRP's emerging proinflammatory role has been progressively extended to include additional target cells, such as neutrophils, lymphocytes, epithelial cells, and endothelial cells. 13-2...

show abstract

Deficiency in cold-inducible RNA-binding protein attenuates acute respiratory distress syndrome induced by intestinal ischemia-reperfusion

Cited by 32 publications

References 37 publications

Plasma Cold-Inducible RNA-Binding Protein Predicts Lung Dysfunction After Cardiovascular Surgery Following Cardiopulmonary Bypass: A Prospective Observational Study

Plasma Cold-Inducible RNA-Binding Protein Predicts Lung Dysfunction After Cardiovascular Surgery Following Cardiopulmonary Bypass: A Prospective Observational Study

Cold-inducible RNA-binding Protein Induces Neutrophil Extracellular Traps in the Lungs during Sepsis

Extracellular CIRP (eCIRP) and inflammation

Contact Info

Product

Resources

About