IL35 Attenuated LPS-Induced Acute Lung Injury by Regulating Macrophage Polarization

Abstract Interleukin 35 (IL35) has been reported to play a role in acute lung injury (ALI); however, the current results on the relationship between IL35 and ALI are inconsistent. Therefore, we will further determine the function of IL35 in mouse ALI and its potential mechanism in this paper. HE staining and Masson staining were used to evaluate lung injury in mice. Immunohistochemical staining was used to calculate the expression of IL35 p35, TLR4 and MD2 and the ratio of Bax/Bcl2 and p-P65/P65. The expression levels of IL35 EBi3, CD68, CD206 and MPO were detected by immunofluorescence staining. RT–PCR was used to examine the expression levels of IL1β and IL6. TUNEL staining was performed to detect apoptotic cells. Overexpression of IL35 alleviated LPS-induced acute lung injury in mice. IL35 overexpression decreased the expression of CD68 and increased the expression of CD206 in ALI mice. Furthermore, upregulation of IL35 expression obviously reduced the expression of MPO, IL1β and IL6 in lung tissues of mice with ALI. Mechanistically, IL35 suppressed the TLR4/NFκB-P65 pathway, leading to the promotion of M1 to M2 macrophage transition and inflammation relief in ALI in mice.

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IL35 Attenuated LPS-Induced Acute Lung Injury by Regulating Macrophage Polarization

10.21203/rs.3.rs-958085/v2 ◽

2022 ◽

Author(s):

Shengsong Chen ◽

Jingen Xia ◽

Yi Zhang ◽

Qingyuan Zhan

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Macrophage Polarization ◽

Tunel Staining ◽

M2 Macrophage ◽

Rt Pcr ◽

Expression Levels ◽

M2 Macrophage Polarization ◽

The Relationship ◽

Masson Staining

Abstract Background Interleukin 35 (IL35) has been reported to play a role in acute lung injury (ALI); however, the current results on the relationship between IL35 and ALI are inconsistent. Therefore, we will further determine the function of IL35 in mouse ALI and its potential mechanism in this paper. Materials and Methods HE staining and Masson staining were used to evaluate lung injury in mice. Immunohistochemical staining was used to calculate the expression of IL35 p35, TLR4 and MD2 and the ratio of Bax/Bcl2 and p-P65/P65. The expression levels of IL35 EBi3, CD68, CD206 and MPO were detected by immunofluorescence staining. RT–PCR was used to examine the expression levels of IL1β and IL6. TUNEL staining was performed to detect apoptotic cells. Results Overexpression of IL35 alleviated LPS-induced acute lung injury in mice. IL35 overexpression decreased the expression of CD68 and increased the expression of CD206 in ALI mice. Furthermore, upregulation of IL35 expression obviously reduced the expression of MPO, IL1β and IL6 in lung tissues of mice with ALI. Mechanistically, IL35 suppressed the TLR4/NFκB-P65 pathway, leading to the promotion of M1 to M2 macrophage transition and inflammation relief in ALI in mice.Conclusions IL35 relieved LPS-reduced inflammation and ALI in mice by regulating M1/M2 macrophage polarization and inhibiting the activation of the TLR4/NFκB-P65 pathway.

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

Frontiers in Immunology ◽

10.3389/fimmu.2021.768435 ◽

2021 ◽

Vol 12 ◽

Author(s):

Wen Zhang ◽

Yao Wang ◽

Chuanwei Li ◽

Yu Xu ◽

Xia Wang ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Rna Binding ◽

Macrophage Polarization ◽

M2 Macrophage ◽

Molecular Pattern ◽

Persistent Inflammation ◽

M1 Phenotype ◽

M2 Macrophage Polarization ◽

Inflammation Resolution

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a condition with an imbalanced inflammatory response and delayed resolution of inflammation. Macrophage polarization plays an important role in inflammation and resolution. However, the mechanism of macrophage polarization in ALI/ARDS is not fully understood. We found that mice with lipopolysaccharide administration developed lung injury with the accumulation of extracellular cold-inducible RNA-binding protein (eCIRP) in the lungs. eCIRP, as a damage-associated molecular pattern (DAMP), inhibited M2 macrophage polarization, thereby tipping the balance toward inflammation rather than resolution. Anti-CIRP antibodies reversed such phenotypes. The levels of macrophage erythropoietin (EPO) receptor (EPOR) were reduced after eCIRP treatment. Myeloid-specific EPOR-deficient mice displayed restrained M2 macrophage polarization and impaired inflammation resolution. Mechanistically, eCIRP impaired Rab26, a member of Ras superfamilies of small G proteins, and reduced the transportation of surface EPOR, which resulted in macrophage polarization toward the M1 phenotype. Moreover, EPO treatment hardly promotes M2 polarization in Rab26 knockout (KO) macrophages through EPOR. Collectively, macrophage EPOR signaling is impaired by eCIRP through Rab26 during ALI/ARDS, leading to the restrained M2 macrophage polarization and delayed inflammation resolution. These findings identify a mechanism of persistent inflammation and a potential therapy during ALI/ARDS.

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Protective effects of recombinant 53-kDa protein of Trichinella spiralis on acute lung injury in mice via alleviating lung pyroptosis by promoting M2 macrophage polarization

Innate Immunity ◽

10.1177/17534259211013397 ◽

2021 ◽

pp. 175342592110133

Author(s):

Ling-yu Wei ◽

An-qi Jiang ◽

Ren Jiang ◽

Si-ying Duan ◽

Xue Xu ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Trichinella Spiralis ◽

Macrophage Polarization ◽

Control Group ◽

M2 Macrophage ◽

Protective Effects ◽

Activated Macrophages ◽

Arginase 1 ◽

M2 Macrophage Polarization

Trichinella spiralis represents an effective treatment for autoimmune and inflammatory diseases. The effects of recombinant T. spiralis (TS) 53-kDa protein (rTsP53) on acute lung injury (ALI) remain unclear. Here, mice were divided randomly into a control group, LPS group, and rTsP53 + LPS group. ALI was induced in BALB/c mice by LPS (10 mg/kg) injected via the tail vein. rTsP53 (200 µl; 0.4 μg/μl) was injected subcutaneously three times at an interval of 5 d before inducing ALI in the rTsP53+LPS group. Lung pathological score, the ratio and markers of classic activated macrophages (M1) and alternatively activated macrophages (M2), cytokine profiles in alveolar lavage fluid, and pyroptosis protein expression in lung tissue were investigated. RTsP53 decreased lung pathological score. Furthermore, rTsP53 suppressed inflammation by increasing IL-4, IL-10, and IL-13. There was an increase in alveolar M2 macrophage numbers, with an increase in CD206 and arginase-1-positive cells and a decrease in alveolar M1 markers such as CD197 and iNOS. In addition, the polarization of M2 macrophages induced by rTsP53 treatment could alleviate ALI by suppressing lung pyroptosis. RTsP53 was identified as a potential agent for treating LPS-induced ALI via alleviating lung pyroptosis by promoting M2 macrophage polarization.

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Maresin1 Promotes M2 Macrophage Polarization Through Peroxisome Proliferator–Activated Receptor-γ Activation to Expedite Resolution of Acute Lung Injury

Journal of Surgical Research ◽

10.1016/j.jss.2020.06.062 ◽

2020 ◽

Vol 256 ◽

pp. 584-594

Author(s):

Nan Qiao ◽

Yun Lin ◽

Zhe Wang ◽

Jia-Yi Chen ◽

Yang-Yang Ge ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Macrophage Polarization ◽

M2 Macrophage ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

M2 Macrophage Polarization

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Exosomal microRNA-16-5p from adipose mesenchymal stem cells promotes TLR4-mediated M2 macrophage polarization in septic lung injury

International Immunopharmacology ◽

10.1016/j.intimp.2021.107835 ◽

2021 ◽

Vol 98 ◽

pp. 107835

Author(s):

Jiakun Tian ◽

Xiaoqian Cui ◽

Jian Sun ◽

Jingxiao Zhang

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Lung Injury ◽

Macrophage Polarization ◽

M2 Macrophage ◽

Adipose Mesenchymal Stem Cells ◽

M2 Macrophage Polarization ◽

Exosomal Microrna

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Emodin protects against intestinal and lung injury induced by acute intestinal injury by modulating SP-A and TLR4/NF-κB pathway

Bioscience Reports ◽

10.1042/bsr20201605 ◽

2020 ◽

Vol 40 (9) ◽

Author(s):

Jingli Qian ◽

Guoping Li ◽

Xiaosheng Jin ◽

Chunfang Ma ◽

Wanru Cai ◽

...

Keyword(s):

Lung Injury ◽

Western Blot ◽

Molecular Mechanisms ◽

Mrna Level ◽

Intestinal Injury ◽

Terminal Deoxynucleotidyl Transferase ◽

Enzyme Linked Immunosorbent Assay ◽

Tunel Staining ◽

Group Model ◽

Expression Levels

Abstract Objective: Our aim was to investigate the effect of emodin on intestinal and lung injury induced by acute intestinal injury in rats and explore potential molecular mechanisms. Methods: Healthy male Sprague–Dawley (SD) rats were randomly divided into five groups (n=10, each group): normal group; saline group; acute intestinal injury model group; model + emodin group; model+NF-κB inhibitor pynolidine dithiocarbamate (PDTC) group. Histopathological changes in intestine/lung tissues were observed by Hematoxylin and Eosin (H&E) and terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling (TUNEL) staining. Serum IKBα, p-IKBα, surfactant protein-A (SP-A) and toll-like receptor 4 (TLR4) levels were examined using enzyme-linked immunosorbent assay (ELISA). RT-qPCR was performed to detect the mRNA expression levels of IKBα, SP-A and TLR4 in intestine/lung tissues. Furthermore, the protein expression levels of IKBα, p-IKBα, SP-A and TLR4 were detected by Western blot. Results: The pathological injury of intestinal/lung tissues was remarkedly ameliorated in models treated with emodin and PDTC. Furthermore, the intestinal/lung injury scores were significantly decreased after emodin or PDTC treatment. TUNEL results showed that both emodin and PDTC treatment distinctly attenuated the apoptosis of intestine/lung tissues induced by acute intestinal injury. At the mRNA level, emodin significantly increased the expression levels of SP-A and decreased the expression levels of IKBα and TLR4 in intestine/lung tissues. According to ELISA and Western blot, emodin remarkedly inhibited the expression of p-IKBα protein and elevated the expression of SP-A and TLR4 in serum and intestine/lung tissues induced by acute intestinal injury. Conclusion: Our findings suggested that emodin could protect against intestinal and lung injury induced by acute intestinal injury by modulating SP-A and TLR4/NF-κB pathway.

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