Extracellular CIRP-Impaired Rab26 Restrains EPOR-Mediated Macrophage Polarization in Acute Lung Injury

Wen, Zhang; Wang, Yao; Li, Chuanwei; Xu, Yü; Wang, Xia; Wu, Di; Gao, Zhan; Qian, Hang; You, Zaichun; Zhang, Zhiren; He, Binfeng; Wang, Guansong

doi:10.3389/fimmu.2021.768435

Cited by 9 publications

(8 citation statements)

References 38 publications

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“…Lately, a study ( 74 ) has revealed the possible regulation pathway of eCIRP in ALI. It was found that the expression of CIRP increased in lung tissues of the LPS-induced ALI/ARDS mice and inhibited the polarization of M2 macrophages and increased the inflammatory response.…”

Section: Role Of Ecirp In Inflammatory Diseasesmentioning

confidence: 99%

Exosome-derived CIRP: An amplifier of inflammatory diseases

Han

Zhang

et al. 2023

Front. Immunol.

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Cold-inducible RNA-binding protein (CIRP) is an intracellular stress-response protein and a type of damage-associated molecular pattern (DAMP) that responds to various stress stimulus by altering its expression and mRNA stability. Upon exposure to ultraviolet (UV) light or low temperature, CIRP get translocated from the nucleus to the cytoplasm through methylation modification and stored in stress granules (SG). During exosome biogenesis, which involves formation of endosomes from the cell membrane through endocytosis, CIRP also gets packaged within the endosomes along with DNA, and RNA and other proteins. Subsequently, intraluminal vesicles (ILVs) are formed following the inward budding of the endosomal membrane, turning the endosomes into multi-vesicle bodies (MVBs). Finally, the MVBs fuse with the cell membrane to form exosomes. As a result, CIRP can also be secreted out of cells through the lysosomal pathway as Extracellular CIRP (eCIRP). Extracellular CIRP (eCIRP) is implicated in various conditions, including sepsis, ischemia-reperfusion damage, lung injury, and neuroinflammation, through the release of exosomes. In addition, CIRP interacts with TLR4, TREM-1, and IL-6R, and therefore are involved in triggering immune and inflammatory responses. Accordingly, eCIRP has been studied as potential novel targets for disease therapy. C23 and M3, polypeptides that oppose eCIRP binding to its receptors, are beneficial in numerous inflammatory illnesses. Some natural molecules such as Luteolin and Emodin can also antagonize CIRP, which play roles similar to C23 in inflammatory responses and inhibit macrophage-mediated inflammation. This review aims to provide a better understanding on CIRP translocation and secretion from the nucleus to the extracellular space and the mechanisms and inhibitory roles of eCIRP in diverse inflammatory illnesses.

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Section: Role Of Ecirp In Inflammatory Diseasesmentioning

confidence: 99%

Exosome-derived CIRP: An amplifier of inflammatory diseases

Han

Zhang

et al. 2023

Front. Immunol.

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“…In this study, we aimed to identify a novel therapeutic approach that can effectively impede the progression of frostbite and expedite recovery with minimal adverse effects. MD2 has been considered as a therapeutic target for various mouse disease models, including acute lung injury, 24 stroke, 17 perioperative neurocognitive disorder, 25 and sepsis 18 , 26 mice models. Besides, CIRP-related peptide has demonstrated effective anti-DAMP damage effects in stroke and sepsis mouse models with low confirmed side effects.…”

Section: Discussionmentioning

confidence: 99%

Tat-CIRP Peptide Facilitates Frozen Wound Healing by Ameliorating Inflammation and Promoting Angiogenesis

Li,

Ding,

et al. 2024

JIR

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Background: Frostbite is a chemia resulting from cold-induced skin damage. The process of frostbite is often accompanied by inflammation, and the therapeutic strategies focusing on anti-inflammation are the main direction to data. Tat-CIRP is a 15 amino acid peptide containing HIV protein and cold-inducible RNA-binding protein (CIRP), which is believed to compete with endogenous CIRP for myeloid differentiation 2 (MD2) binding. This study aims to investigate the efficacy of Tat-CIRP in the treatment of frostbite. Methods: A mouse model of frostbite was established, and on the first day after frostbite occurrence, Tat-CIRP peptide was administered intravenously via the tail with a dosage interval of one day for a total of three doses. Frozen mouse skin sections were subjected to histological analysis, including hematoxylin-eosin (HE) staining, Masson staining, and immunohistochemical examination. Western blotting was performed to detect the expression level of Ki-67 in mouse skin tissue. Results: One day after frostbite, mice exhibited skin swelling and a solid appearance. From day 1 to 5 after frostbite, MD2 expression was significantly upregulated, while CIRP expression was downregulated. Compared to the frostbite group, mice treated with Tat-CIRP showed accelerated frostbite recovery, reduced levels of inflammatory factors and MD2. Furthermore, the expression of cell proliferation-associated protein Ki-67 and angiogenesis-related protein CD31 was upregulated. Conclusion: Tat-CIRP promotes frozen wound healing via inhibiting inflammation and promoting angiogenesis in frostbitten mice.

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“… 19 Macrophage erythropoietin receptor signaling is impaired by eCIRP through Rab26 during acute lung injury/acute respiratory distress syndrome, leading to restrained M2 macrophage polarization and delayed resolution of inflammation. 20 Furthermore, eCIRP dysregulates macrophage bacterial phagocytosis during sepsis. 21 Intravenous injection of recombinant murine CIRP in C57BL/6 mice causes lung injury, as evidenced by vascular leakage, edema, increased leukocyte infiltration, and cytokine production in the lung tissue, accompanied by endothelial cell activation and pyroptosis in isolated primary mouse lung vascular endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

Associations of cold‐inducible RNA‐binding protein with bacterial load, proinflammatory cytokines and mortality from pneumonia

Guo,

Li,

Zeng

et al. 2024

Clinical Translational Sci

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Cold‐inducible RNA‐binding protein (CIRP) is a damage‐associated molecular pattern that plays a critical role in triggering inflammatory responses. It remains unknown whether CIRP is strongly associated with bacterial load, inflammatory response, and mortality in sepsis model. Pneumonia was induced in specific pathogen‐free 8–9‐week old male rats by injecting bacteria via puncture of the tracheal cartilage. The expressions of CIRP and proinflammatory cytokines [tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6) and IL‐1β] in lung tissues, alveolar macrophages (AMs), plasma, and bronchoalveolar lavage fluid (BALF) were determined by reverse transcription‐polymerase chain reaction, western blotting, and enzyme‐linked immunosorbent assay. The numbers of bacteria recovered from the lungs were correlated with the bacterial loads injected and mortality. The expressions of CIRP increased sharply as the bacterial loads increased in the lung tissues and AMs. The amounts of TNF‐α, IL‐6 and IL‐1β proteins synthesized were dependent on the bacterial load in the lung tissues. Releases of CIRP, TNF‐α, IL‐6, and IL‐1β increased with the bacterial load in the blood plasma. The proteins confirmed similar patterns in the BALF. CIRP was strongly associated with the releases of TNF‐α, IL‐6, and IL‐1β in the lung tissues, blood plasma, and BALF, and showed a close correlation with mortality. CIRP demonstrated a strong association with bacterial load, which is new evidence, and close correlations with proinflammatory cytokines and mortality of pneumonia in rats, suggesting that it might be an interesting pneumonic biomarker for monitoring host response and predicting mortality, and a promising target for immunotherapy.

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Extracellular CIRP-Impaired Rab26 Restrains EPOR-Mediated Macrophage Polarization in Acute Lung Injury

Cited by 9 publications

References 38 publications

Exosome-derived CIRP: An amplifier of inflammatory diseases

Exosome-derived CIRP: An amplifier of inflammatory diseases

Tat-CIRP Peptide Facilitates Frozen Wound Healing by Ameliorating Inflammation and Promoting Angiogenesis

Associations of cold‐inducible RNA‐binding protein with bacterial load, proinflammatory cytokines and mortality from pneumonia

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