PAI-1 inhibits development of chronic otitis media and tympanosclerosis in a mouse model of otitis media

Shin, Seul Gi; Koh, Seo Hyun; Woo, Chang Hoon; Lim, Jae Hyang

doi:10.3109/00016489.2014.940554

Cited by 13 publications

(14 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Reaction was amplified and quantified by using StepOne Plus (Life Technologies) according to the manufacturer's instructions as described previously (15,31,39,40). Relative quantity (RQ) of mouse IL-1β mRNA expression was obtained by using the comparative threshold cycle (Ct) Method and was normalized using mouse glyceraldehydes-3-phosphate dehydrogenase (GAPDH) as endogenous control.…”

Section: Real-time Quantitative Rt-pcr (Q-pcr) Assaymentioning

confidence: 99%

See 1 more Smart Citation

Interleukin-1β Participates in the Development of Pneumococcal Acute Lung Injury and Death by Promoting Alveolar Microvascular Leakage

et al. 2015

Self Cite

View full text Add to dashboard Cite

Streptococcus pneumoniae (S. pneumoniae, also known as pneumococcus) infections are major causes of death worldwide. Despite the development and use of effective antibiotics, high, early mortality due to pneumococcal infections has not been decreased for the last few decades. Recent study found a deadly hemorrhagic acute lung injury (ALI) as a major cause of death at the early stage of severe pneumococcal infections. Interleukin (IL)-1β was known to play critical roles not only for the development of ALI but also resolution of it. The role of IL-1β on the pathogenesis of pneumococcal ALI, however, has not been well understood yet. This study aims to investigate the role of IL-1β on the development of pneumococcal ALI and subsequent death. IL-1β expression was upregulated in the lungs of pneumococcal ALI in wild-type (WT) mice, but not in the plasma. Despite an increased expression of pulmonary IL-1β, no inflammatory cell infiltration into airway has been observed. Upregulation of IL-1β expression was indeed dependent on pneumococcal cytoplasmic toxin pneumolysin and its cell surface receptor Toll-like receptor 4. Deficiency of IL-1R1, a cell surface receptor of IL-1β, resulted in a markedly reduced hemorrhagic pulmonary edema and early death in pneumococcal ALI. Finally, IL-1β neutralization in WT mice protects against pulmonary hemorrhagic edema and death. These data suggest that pulmonary expression of IL-1β exacerbates pneumolysin-induced ALI and death by promoting alveolar hemorrhagic edema.

show abstract

Section: Real-time Quantitative Rt-pcr (Q-pcr) Assaymentioning

confidence: 99%

“…Relative quantity (RQ) of mouse IL-1β mRNA expression was obtained by using the comparative threshold cycle (Ct) Method and was normalized using mouse glyceraldehydes-3-phosphate dehydrogenase (GAPDH) as endogenous control. Primers for mouse IL-1β and GAPDH were described previously (39,40).…”

Section: Real-time Quantitative Rt-pcr (Q-pcr) Assaymentioning

confidence: 99%

Interleukin-1β Participates in the Development of Pneumococcal Acute Lung Injury and Death by Promoting Alveolar Microvascular Leakage

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…Plasminogen activator inhibitor (PAI-1) is a member of the serine protease inhibitor protein family ( 26 ). PAI-1 knockout mice exhibited low levels of inflammation compared with wild-type mice ( 27 ), indicating that this protein may serve a role in the inflammatory response. Furthermore, a previous study indicated that the PAI-1 level was closely associated with BC metastasis ( 28 ).…”

Section: Introductionmentioning

confidence: 99%

Ginseng polysaccharide inhibits MDA‑MB‑231 cell proliferation by activating the inflammatory response

et al. 2020

View full text Add to dashboard Cite

Ginseng polysaccharide (GPS) is known for its efficacy in cancer therapy; however, its regulatory mechanism in breast cancer (BC) remains unclear. To analyze the effect of GPS on BC cell proliferation, cell proliferation rate calculations, western blotting, plasmid transfections, electrophoretic mobility shift assays and chromatin immunoprecipitation assays were performed. GPS treatment in the culture cell medium inhibited cell proliferation in the BC cell line MDA-MB-231. In addition, the E-cadherin level was enhanced while the vimentin level was suppressed following GPS treatment (both P<0.05). Furthermore, the levels of apoptotic markers, including cleaved-Caspase-3 and p53, and inflammatory response markers, including plasminogen activator inhibitor and TNF-α, were induced by GPS treatment in MDA-MB-231 cells (all P<0.05). These results indicated that GPS supplementation activated the inflammatory response and apoptosis in BC cells. GPS treatment activated the phosphorylation levels of c-Jun N-terminal kinase, Akt and NF-κB. In MDA-MB-231 cells, GPS resulted in the accumulation of the NF-κB components p65, p50 and Ikaros family zing finger protein 1 (IKZF1; all, P<0.05). Chromatin immunoprecipitation and electrophoretic mobility shift assays indicated that p65 bound to the IKZF1 promoter. The overexpression of IKZF1 or p65 inhibited MDA-MB-231 cell proliferation (P<0.05), indicating that GPS treatment may inhibit BC cell proliferation by the activation of IKZF1. Taken together, these results suggested that GPS significantly inhibited BC cell proliferation via the control of the biological processes, including the activation of p65-IKZF1 signaling and apoptosis. The data indicated a novel mechanism for further understanding of cancer cell proliferation.

show abstract

“…There is also evidence of the involvement of signaling pathways and inflammatory factors involved in OM. Pai-1 knockout mice showed significant pathological changes of tympanosclerosis (Shin et al, 2014); mice deficient in the C5a gene have been shown to have reduced levels of IL-6, mKC, and MCP-1, in association with decrease in inflammatory cell recruitment, mucosal inflammation, and bacterial clearance (Tong et al, 2014); mice lacking the IL-17A gene, encoding interleukin 17A (IL-17A), a neutrophil inducing factor, were associated with abnormal recruitment and apoptosis of neutrophils (Wang et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Recent Perspectives on Gene-Microbe Interactions Determining Predisposition to Otitis Media

et al. 2019

View full text Add to dashboard Cite

A comprehensive understanding about the pathogenesis of otitis media (OM), one of the most common pediatric diseases, has the potential to alleviate a substantial disease burden across the globe. Advancements in genetic and bioinformatic detection methods, as well as a growing interest in the microbiome, has enhanced the capability of researchers to investigate the interplay between host genes, host microbiome, invading bacteria, and resulting OM susceptibility. Early studies deciphering the role of genetics in OM susceptibility assessed the heritability of the phenotype in twin and triplet studies, followed by linkage studies, candidate gene approaches, and genome-wide association studies that have helped in the identification of specific loci. With the advancements in techniques, various chromosomal regions and genes such as FBXO11, TGIF1, FUT2, FNDC1, and others have been implicated in predisposition to OM, yet questions still remain as to whether these implicated genes truly play a causative role in OM and to what extent. Meanwhile, 16S ribosomal RNA (rRNA) sequencing, microbial quantitative trait loci (mbQTL), and microbial genome-wide association studies (mGWAS) have mapped the microbiome of upper airways sites and therefore helped in enabling a more detailed study of interactions between host polymorphisms and host microbiome composition. Variants of specific genes conferring increased OM susceptibility, such as A2ML1, have also been shown to influence the microbial composition of the outer and middle ear in patients with OM, suggesting their role as mediators of disease. These interactions appear to impact the colonization of known otopathogens (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis), as well as Neisseria, Gemella, Porphyromonas, Alloprevotella, and Fusobacterium populations that have also been implicated in OM pathogenesis. Meanwhile, studies demonstrating an increased abundance of Dolosigranulum and Corynebacterium in healthy patients compared to those with OM suggest a protective role for these bacteria, thereby introducing potential avenues for future probiotic treatment. Incorporating insights from these genetic, microbiome, and host-pathogen studies will allow for a more robust, comprehensive understanding of OM pathogenesis that can ultimately facilitate in the development of exciting new treatment modalities.

show abstract

PAI-1 inhibits development of chronic otitis media and tympanosclerosis in a mouse model of otitis media

Cited by 13 publications

References 19 publications

Interleukin-1β Participates in the Development of Pneumococcal Acute Lung Injury and Death by Promoting Alveolar Microvascular Leakage

Interleukin-1β Participates in the Development of Pneumococcal Acute Lung Injury and Death by Promoting Alveolar Microvascular Leakage

Ginseng polysaccharide inhibits MDA‑MB‑231 cell proliferation by activating the inflammatory response

Recent Perspectives on Gene-Microbe Interactions Determining Predisposition to Otitis Media

Contact Info

Product

Resources

About