Differential modulation of pulmonary caspases: Is this the key to Ureaplasma-driven chronic inflammation?

Silwedel, Christine; Fehrholz, Markus; Speer, Christian P.; Ruf, Katharina; Manig, Steffi; Glaser, Kirsten

doi:10.1371/journal.pone.0216569

Cited by 6 publications

(8 citation statements)

References 78 publications

(83 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies on Ureaplasma spp. showed similar results; Wolfs et al showed there was no induction of apoptosis in enterocytes, while Silwedel et al reported endothelial cells (Wolfs et al 2013, Silwedel et al 2019. Several intracellular bacteria inhibit host cell apoptosis so they can persistently colonize the cells, which can facilitate their dissemination (Behar & Briken 2019, FitzGerald et al 2020.…”

Section: Discussionmentioning

confidence: 94%

Inflammatory response elicited by Ureaplasma parvum colonization in human cervical epithelial, stromal, and immune cells

et al. 2022

View full text Add to dashboard Cite

Ureaplasma parvum is a commensal bacterium in the female reproductive tract but has been associated with pregnancy complications such as preterm prelabor rupture of membranes and preterm birth (PTB). However, the pathologic effects of U. parvum in the cervix, that prevents ascending infections during pregnancy, are still poorly understood. To determine the impact of U. parvum on the cervix, ectocervical (ecto) and endocervical (endo) epithelial and stromal cells were incubated with U. parvum. Macrophages were also tested as a proxy for cervical macrophages to determine the antigenicity of U. parvum. The effects of U. parvum, including influence on cell cycle and cell death, antimicrobial peptide production, epithelial-to-mesenchymal transition (EMT), and inflammatory cytokine levels, were assessed. U. parvum colonized cervical epithelial and stromal cells 4 hours post-infection. Like uninfected control, U. parvum neither inhibited cell cycle progression and nor caused cell death in cervical epithelial and stromal cells. U. parvum increased the production of the antimicrobial peptides (AMPs) cathelicidin and human β-defensin 3 and exhibited weak signs of EMT evidenced by decreased cytokeratin 18 and increased vimentin expression in cervical epithelial cells. U. parvum induced a pro-inflammatory environment (cytokines) and increased MMP-9 in cervical epithelial cells but promoted pro- and anti-inflammatory responses in cervical stromal cells and macrophages. U. parvum may colonize the cervical epithelial layer, but induction of AMPs and anti-inflammatory response may protect the cervix and may prevent ascending infections that can cause PTB. These findings suggest that U. parvum is a weak inducer of inflammation in the cervix.

show abstract

Section: Discussionmentioning

confidence: 94%

Inflammatory response elicited by Ureaplasma parvum colonization in human cervical epithelial, stromal, and immune cells

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Increased oxidative stress plays a key role in the progression of the inflammatory process. It has been shown that lung cells release these cytokines in response to oxidative stress 24,44 . Our study has demonstrated that pups in the control and APO groups had lower mean levels of TNF‐α, IL‐1β in lung tissue along with fewer alveolar macrophages than the pups in the BPD group.…”

Section: Discussionmentioning

confidence: 48%

“…It has been shown that lung cells release these cytokines in response to oxidative stress. 24,44 Our study has demonstrated that pups in the control and APO groups had lower mean levels of TNF-α, IL-1β in lung tissue along with fewer alveolar macrophages than the pups in the BPD group. More importantly, we have observed that mean levels of TNF-α, IL-1β in lung tissue, and the mean alveolar macrophage score significantly decreased in the rats after APO treatment (Figures 4 and 7).…”

Section: F I G U R E 2 the Bpd Group Demonstrating Thickness Of Alveo...mentioning

confidence: 72%

The protective effects of apocynin in hyperoxic lung injury in neonatal rats

Оздемир

Gökçe

Tekin

et al. 2021

Pediatric Pulmonology

View full text Add to dashboard Cite

Aim: Inflammation and oxidate stress are significant factors in the pathogenesis of bronchopulmonary dysplasia (BPD). The aim of this study is to investigate the efficacy of apocynin (APO), an anti-inflammatory, antioxidant, and antiapoptotic drug, in the prophylaxis of neonatal hyperoxic lung injury.Method: This experimental study included 40 neonatal rats divided into the control, APO, BPD, and BPD + APO groups. The control and APO groups were kept in a normal room environment, while the BPD and BPD + APO groups were kept in a hyperoxic environment. The rats in the APO and BPD + APO groups were administered intraperitoneal APO, while the control and BPD rats were administered ordinary saline. At the end of the trial, lung tissue was evaluated with respect to the degree of histopathological injury, apoptosis, oxidant and antioxidant capacity, and severity of inflammation. Result:The BPD and BPD + APO groups exhibited higher mean histopathological injury and alveolar macrophage scores compared to the control and APO groups.Both scores were lower in the BPD + APO group in comparison to the BPD group.The BPD + APO group had a significantly lower average of TUNEL positive cells than the BPD group. The lung tissue examination indicated significantly higher levels of mean malondialdehyde (MDA), total oxidant status (TOS), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in the BPD group compared to the control and APO groups. While the TNF-α and IL-1β levels of the BPD + APO group were similar to that of the control group, the MDA and TOS levels were higher compared to the controls and lower compared to the BPD group. The BPD group demonstrated significantly lower levels/activities of mean total antioxidant status, glutathione reductase, superoxide dismutase, glutathione peroxidase in comparison to the control and APO groups. While the mean antioxidant enzyme activity of the BPD + APO group was lower than the control group, it was significantly higher compared to the BPD group. Conclusion:This is the first study in the literature to reveal through an experimental neonatal hyperoxic lung injury that APO, an anti-inflammatory, antioxidant, and antiapoptotic drug, exhibits protective properties against the development of BPD.

show abstract

“…infections in pulmonary epithelial cells led to the downregulation of caspase mRNA, suppressing apoptosis, and showed limited cytokine response. 56 Another study on Ureaplasma diversum infection in Hep-2 cells revealed a lower number of apoptotic cells and decreased expression of pro-apoptotic genes compared to uninfected control. 57 Interestingly, a recent study demonstrated that a novel virulence factor from Ureaplasma (UpVF) triggered endoplasmic reticulum stress but suppressed the apoptotic cascade in HeLa cells, leading to increased resistance to anticancer treatments.…”

Section: Discussionmentioning

confidence: 98%

“…Similarly, Ureaplasma spp. infections in pulmonary epithelial cells led to the downregulation of caspase mRNA, suppressing apoptosis, and showed limited cytokine response 56 . Another study on Ureaplasma diversum infection in Hep‐2 cells revealed a lower number of apoptotic cells and decreased expression of pro‐apoptotic genes compared to uninfected control 57 .…”

Section: Discussionmentioning

confidence: 99%

Effects of Ureaplasma parvum infection in the exosome biogenesis‐related proteins in ectocervical epithelial cells

Tantengco,

Menon

2023

American J Rep Immunol

View full text Add to dashboard Cite

Ureaplasma parvum is a mycoplasma commonly associated with female reproductive pathologies, such as preterm birth and infertility. It can survive intracellularly and utilize exosomes to propagate infection and its virulence factors. This study explored the differential protein composition of exosomes derived from normal and U. parvum‐infected cells. We also investigated the impact of U. parvum on exosome biogenesis in ectocervical epithelial cells. Ectocervical epithelial (ECTO) cells were infected with U. parvum, and immunocytochemical staining was performed using U. parvum‐specific marker multiple banded antigen (mba) and exosome marker CD9. NanoLC–MS/MS analysis was conducted to identify differentially expressed proteins in exosomes. Ingenuity Pathway Analysis (IPA) was performed to identify affected canonical pathways and biological functions associated with the protein cargo of exosomes. Western blot analysis of ECTO cells validated the proteomic findings in ECTO cells. U. parvum exhibited colonization of ECTO cells and colocalization with CD9‐positive intraluminal vesicles. Proteomic analysis revealed decreased protein abundance and distinct protein profiles in exosomes derived from U. parvum‐infected ECTO cells. Differentially expressed proteins were associated with clathrin‐mediated endocytosis and various signaling pathways indicative of infection, inflammation, and cell death processes. Additionally, U. parvum infection altered proteins involved in exosome biogenesis. In ECTO cells, U. parvum infection significantly decreased clathrin, ALIX, CD9, and CD63 and significantly increased TSG101, Rab5, Rab35, and UGCG. These findings contribute to our understanding of the infection mechanism and shed light on the importance of exosome‐mediated communication in the pathophysiology of diseases affecting the cervix, such as cervicitis and preterm birth.

show abstract

Differential modulation of pulmonary caspases: Is this the key to Ureaplasma-driven chronic inflammation?

Cited by 6 publications

References 78 publications

Inflammatory response elicited by Ureaplasma parvum colonization in human cervical epithelial, stromal, and immune cells

Inflammatory response elicited by Ureaplasma parvum colonization in human cervical epithelial, stromal, and immune cells

The protective effects of apocynin in hyperoxic lung injury in neonatal rats

Effects of Ureaplasma parvum infection in the exosome biogenesis‐related proteins in ectocervical epithelial cells

Contact Info

Product

Resources

About