UFM1 inhibits the activation of the pyroptosis in LPS-induced goat endometritis

Wang, Zongjie; Huang, Shan; Xue, Zhongqiang; Gao, Kangkang; Sun, Min; Wang, Aihua; Lin, Peng; Jin, Yaping

doi:10.1016/j.theriogenology.2022.09.018

Cited by 6 publications

(1 citation statement)

References 32 publications

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“…Related studies [15,16] have shown that the combined use of ceftriaxone, doxycycline and metronidazole in the treatment of acute pelvic inflammatory disease is significantly more effective than when these antibiotics were used individually. Pyroptosis has been proved to be related to the progression of endometritis in many animal models [17][18][19], but the underlying mechanism remains largely uncharacterized.…”

Section: Combinationmentioning

confidence: 99%

Combination of Doxycycline with Metronidazole Protects against Pyroptosis in Rats with Endometritis through the Modulation of TLR4/NF-κB Pathway

Yao,

Lin,

Yang

et al. 2024

Discovery Medicine

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Background: Endometritis is a condition usually resulted from the bacterial infection of uterus, causing pelvic disease, sepsis, shock, uterine necrosis and even death if it is inappropriately treated. The aim of this study is to explore the pathogenesis of endometritis, and investigate whether the combination of doxycycline and metronidazole offers stronger protection against lipopolysaccharide (LPS)-induced endometritis, and decipher more about the mechanisms underlying endometritis-related pyroptosis. Methods: Sprague-Dawley (SD) rats were divided into five groups (n = 8 per group): control, model, metronidazole, doxycycline, and combination groups. In control group, the rats were injected with saline, while in other groups, lipopolysaccharide was injected into uterus of the rats to establish endometritis. Hematoxylin-eosin ( H&E) staining was performed as part of the histopathological examination of endometrium. The integrity of chromatin and pyroptosis were evaluated by terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) assay. Western blot and quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) were performed to ascertain the activation of toll-like receptors (TLR4)/nuclear factor-kappa B (NF-κB) pathway by detecting protein levels of phosphorylated p50 (p-p50)/p50, phosphorylated nuclear factor-kappa B (p-NF-κB)/NF-κB, phosphorylated IkappaB (p-IκB), and TLR4 protein and mRNA. Development of pyroptosis was also detected by determining the levels of caspase-1 and caspase-5 through Western blot and qRT-PCR. Enzymelinked immunosorbent assay (ELISA) was used to detect levels of interleukin (IL)-1β, IL-18, IL-2, IL-4, IL-6 and tumor necrosis factor alpha (TNF-α), and flow cytometry was adopted to determine T-helper (Th)1 and Th2 cell percentage to assess the extent of pyroptosis and Th1/Th2 imbalance. Results: The uterine of the model group exhibited pathological alterations and higher degree of cell apoptosis. Compared with the control rats, model group showed lower protein levels of p-p50/p50 (p < 0.001), p-NF-κB/NF-κB (p < 0.001), p-IκB (p < 0.001), and TLR4 protein (p < 0.001) and mRNA (p < 0.001). Elevated levels of caspase-1 (p < 0.001), caspase-5 (p < 0.001), IL-1β (p < 0.001), IL-18 (p < 0.001), IL-2 (p < 0.01), TNF-α (p < 0.05) and Th1/Th2 (p < 0.001) as well as reduced levels of IL-4 (p < 0.05) and IL-6 (p < 0.01) were observed in the model group, which could however be reversed by metronidazole (p < 0.01) or doxycycline (p < 0.01), with a more significant effect detected if a combination of the two drugs was administered (p < 0.01). Conclusions: The combination of doxycycline and metronidazole protects against rat endometritis by inhibiting TLR4/NF-κB pathway-mediated inflammation and suppressing pyroptosis.

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Section: Combinationmentioning

confidence: 99%

Combination of Doxycycline with Metronidazole Protects against Pyroptosis in Rats with Endometritis through the Modulation of TLR4/NF-κB Pathway

Yao,

Lin,

Yang

et al. 2024

Discovery Medicine

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The emerging roles of UFMylation in the modulation of immune responses

Liang,

Ning,

Wang

et al. 2024

Clinical & Translational Med

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Post‐translational modification is a rite of passage for cellular functional proteins and ultimately regulate almost all aspects of life. Ubiquitin‐fold modifier 1 (UFM1) system represents a newly identified ubiquitin‐like modification system with indispensable biological functions, and the underlying biological mechanisms remain largely undiscovered. The field has recently experienced a rapid growth of research revealing that UFMylation directly or indirectly regulates multiple immune processes. Here, we summarised important advances that how UFMylation system responds to intrinsic and extrinsic stresses under certain physiological or pathological conditions and safeguards immune homeostasis, providing novel perspectives into the regulatory framework and functions of UFMylation system, and its therapeutic applications in human diseases.

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