Incomplete Knockdown of MyD88 Inhibits LPS-Induced Lung Injury and Lung Fibrosis in a Mouse Model
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature..
Acute lung injury (ALI) is a life-threatening disorder stemmed mainly from an uncontrolled inflammatory response. Lipopolysaccharide (LPS) is commonly used to induce ALI animal models. Toll-like receptor 4 (TLR4) is the main receptor for LPS, and myeloid differentiation factor 88 (MyD88) is a key adaptor protein molecule in the Toll-like receptor (TLR) signaling pathway. Thus, MyD88 knockdown heterozygous mice (MyD88+/-) were used to investigate the effect of incomplete knockout of the MyD88 gene on indirect LPS-induced ALI through intraperitoneal injection of LPS. The LPS-induced ALI significantly upregulated MyD88 expression, and heterozygous mice with incomplete knockout of the MyD88 gene (MyD88+/-) ameliorated LPS-induced histopathological injury and collagen fiber deposition. Heterozygous mice with incomplete knockout of the MyD88 gene (MyD88+/-) inhibited LPS-induced nuclear factor-κB (NF-κB) pathway activation, but TLR-4 expression tended to be upregulated. Incomplete knockdown of the MyD88 gene also downregulated LPS-induced expression of IL1-β, IL-6, TNF-α, TGF-β, SMAD2, and α-SMA. The transcriptome sequencing also revealed significant changes in LPS-regulated genes (such as IL-17 signaling pathway genes) after the incomplete knockdown of MyD88. In conclusion, this paper clarified that LPS activates the downstream NF-κB pathway depending on the MyD88 signaling pathway, which induces the secretion of inflammatory cytokines such as IL-1β/IL-6/TNF-α and ultimately triggers ALI. Incomplete knockdown of the MyD88 reverses LPS-induced lung fibrosis, which confirmed the vital role of MyD88 in LPS-induced ALI.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:46 |
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| Enthalten in: |
Inflammation - 46(2023), 6 vom: 18. Dez., Seite 2276-2288 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Fan, Hui [VerfasserIn] |
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| Links: |
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| Themen: |
Acute lung injury |
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| Anmerkungen: |
Date Completed 30.11.2023 Date Revised 30.11.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s10753-023-01877-4 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Acute lung injury (ALI) is a life-threatening disorder stemmed mainly from an uncontrolled inflammatory response. Lipopolysaccharide (LPS) is commonly used to induce ALI animal models. Toll-like receptor 4 (TLR4) is the main receptor for LPS, and myeloid differentiation factor 88 (MyD88) is a key adaptor protein molecule in the Toll-like receptor (TLR) signaling pathway. Thus, MyD88 knockdown heterozygous mice (MyD88+/-) were used to investigate the effect of incomplete knockout of the MyD88 gene on indirect LPS-induced ALI through intraperitoneal injection of LPS. The LPS-induced ALI significantly upregulated MyD88 expression, and heterozygous mice with incomplete knockout of the MyD88 gene (MyD88+/-) ameliorated LPS-induced histopathological injury and collagen fiber deposition. Heterozygous mice with incomplete knockout of the MyD88 gene (MyD88+/-) inhibited LPS-induced nuclear factor-κB (NF-κB) pathway activation, but TLR-4 expression tended to be upregulated. Incomplete knockdown of the MyD88 gene also downregulated LPS-induced expression of IL1-β, IL-6, TNF-α, TGF-β, SMAD2, and α-SMA. The transcriptome sequencing also revealed significant changes in LPS-regulated genes (such as IL-17 signaling pathway genes) after the incomplete knockdown of MyD88. In conclusion, this paper clarified that LPS activates the downstream NF-κB pathway depending on the MyD88 signaling pathway, which induces the secretion of inflammatory cytokines such as IL-1β/IL-6/TNF-α and ultimately triggers ALI. Incomplete knockdown of the MyD88 reverses LPS-induced lung fibrosis, which confirmed the vital role of MyD88 in LPS-induced ALI | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Deng, Chong |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Guozhong |e verfasserin |4 aut | |
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