The high-mobility group protein B1–Toll-like receptor 4 pathway contributes to the acute lung injury induced by bilateral nephrectomy

During cardiopulmonary bypass (CPB), pulmonary ischemia/reperfusion (I/R) injury can cause acute lung injury (ALI). Our previous research confirmed that abnormal high-mobility group box 1 (HMGB1) release after CPB was closely related to ALI. However, the mechanism underlying the HMGB1-mediated induction of ALI after CPB is unclear. Our previous study found that HMGB1 binds Toll-like receptor 4 (TLR4), leading to lung injury, but direct evidence of a role for these proteins in the mechanism of CPB-induced lung injury has not been shown. We examined the effects of inhibiting HMGB1 or reducing TLR4 expression on CPB-induced lung injury in rats administered anti-HMBG1 antibody or TLR4 short-hairpin RNA (shTLR4), respectively. In these rat lungs, we studied the histologic changes and levels of interleukin- (IL-) 1β, tumour necrosis factor- (TNF-) α, HMGB1, and TLR4 after CPB. After CPB, the lung tissues from untreated rats showed histologic features of injury and significantly elevated levels of IL-1β, TNF-α, HMGB1, and TLR4. Treatment with anti-HMGB1 attenuated the CPB-induced morphological inflammatory response and protein levels of IL-1β, TNF-α, HMGB1, and TLR4 in the lung tissues and eventually alleviated the ALI after CPB. Treatment with shTLR4 attenuated the CPB-induced morphological inflammatory response and protein levels of IL-1β, TNF-α, and TLR4 in the lung tissues and eventually alleviated the ALI after CPB, but could not alleviate the HMGB1 protein levels induced by CPB. In summary, the present study demonstrated that the HMGB1/TLR4 pathway mediated the development of ALI induced by CPB.

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Dexmedetomidine Post-Conditioning Alleviates Cerebral Ischemia-Reperfusion Injury in Rats by Inhibiting High Mobility Group Protein B1 Group (HMGB1)/Toll-Like Receptor 4 (TLR4)/Nuclear Factor kappa B (NF-κB) Signaling Pathway

Medical Science Monitor ◽

10.12659/msm.918617 ◽

2020 ◽

Vol 26 ◽

Cited By ~ 3

Author(s):

Yongyi Zhai ◽

Yulin Zhu ◽

Jingying Liu ◽

Kun Xie ◽

Jingui Yu ◽

...

Keyword(s):

Nuclear Factor Kappa B ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

High Mobility ◽

Nuclear Factor ◽

Toll Like Receptor ◽

High Mobility Group Protein ◽

Toll Like Receptor 4 ◽

Cerebral Ischemia Reperfusion Injury ◽

Group Protein

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High Mobility Group Protein HMG-R

10.32388/nb6yys ◽

2020 ◽

Author(s):

Keyword(s):

High Mobility ◽

High Mobility Group ◽

High Mobility Group Protein ◽

Group Protein

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Faculty Opinions recommendation of Actively transcribed rRNA genes in S. cerevisiae are organized in a specialized chromatin associated with the high-mobility group protein Hmo1 and are largely devoid of histone molecules.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1144960.602064 ◽

2009 ◽

Author(s):

Jim Maher

Keyword(s):

High Mobility ◽

High Mobility Group ◽

Rrna Genes ◽

High Mobility Group Protein ◽

Group Protein

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Chelidonine Attenuates Sepsis-Induced Acute Lung Injury via Suppressing Toll-like Receptor 4/Myeloid Differentiation Factor 88/Nuclear Factor-॔B Signaling Pathway in Newborn Mice

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.19:120-126 ◽

2020 ◽

Vol 19 (1) ◽

pp. 120-126

Author(s):

Ayinuerguli Adili ◽

Adilijiang Kari ◽

Chuanlong Song ◽

Abulaiti Abuduhaer

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Nuclear Factor Kappa B ◽

Myeloid Differentiation ◽

Nuclear Factor ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Inflammatory Infiltration ◽

Newborn Mice ◽

Myeloid Differentiation Factor

We have examined the mechanism underlying amelioration of sepsis-induced acute lung injury by chelidonine in newborn mice. To this end, a sepsis model was established using cecal ligation and puncture in newborn mice. The sepsis-induced acute lung injury was associated with an increased inflammatory infiltration and pulmonary congestion, as well as abnormal alveolar morphology. The lung injury-associated increased tumor necrosis factor-α and interleukin-1β in bronchoalveolar lavage fluid and lung, the markers of inflammatory infiltration and pulmonary congestion, diminished by chelidonine treatment. Chelidonine administration also downregulated protein levels of toll-like receptor 4, myeloid differentiation factor 88, phosphorylated nuclear factor-kappa B, and nuclear factor-kappa B that are elevated in response to sepsis. In conclusion, chelidonine provides a potential therapeutic strategy for newborn mice with acute lung injury.

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Juglone Attenuates Sepsis-Induced Acute Lung Injury via Suppression of the TLR4/Nf-κb Pathway

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.18:201-206 ◽

2020 ◽

Vol 18 (2) ◽

pp. 201-206

Author(s):

Qiu Nan ◽

Xu Xinmei ◽

He Yingying ◽

Fan Chengfen

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Nuclear Factor Kappa B ◽

Cecal Ligation ◽

Myeloperoxidase Activity ◽

Nuclear Factor ◽

Cecal Ligation And Puncture ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Nuclear Factor Kappa

Sepsis, with high mortality, induces deleterious organ dysfunction and acute lung injury. Natural compounds show protective effect against sepsis-induced acute lung injury. Juglone, a natural naphthoquinone, demonstrates pharmacological actions as a pro-apoptotic substrate in tumor treatment and anti-inflammation substrate in organ injury. In this study, the influence of juglone on sepsis-induced acute lung injury was investigated. First, a septic mice model was established via cecal ligation and puncture, and then verified via histopathological analysis of lung tissues, the wet/dry mass ratio and myeloperoxidase activity was determined. Cecal ligation and puncture could induce acute lung injury in septic mice, as demonstrated by alveolar damage and increase of wet/dry mass ratio and myeloperoxidase activity. However, intragastric administration juglone attenuated cecal ligation and puncture-induced acute lung injury. Secondly, cecal ligation and puncture-induced increase of inflammatory cells in bronchoalveolar lavage fluid was also alleviated by the administration of juglone. Similarly, the protective effect of juglone against cecal ligation and puncture-induced acute lung injury was accompanied by a reduction of pro-inflammatory factor secretion in bronchoalveolar lavage fluid and lung tissues. Cecal ligation and puncture could activate toll-like receptor 4/nuclear factor-kappa B signaling pathway, and administration of juglone suppressed toll-like receptor 4/nuclear factor-kappa B activation. In conclusion, juglone attenuated cecal ligation and puncture-induced lung damage and inflammatory response through inactivation of toll-like receptor 4/nuclear factor-kappa B, suggesting a potential therapeutic strategy in the treatment of sepsis-induced acute lung injury.

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