Mutation in Fbxo11 Leads to Altered Immune Cell Content in Jeff Mouse Model of Otitis Media

Vikhe, Pratik P.; Tateossian, Hilda; Bharj, Gurpreet; Brown, Steve; Hood, Derek W.

doi:10.3389/fgene.2020.00050

Cited by 8 publications

(9 citation statements)

References 35 publications

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“…In the current study we found no statistical differences in the leukograms and only minimal changes for spleen WBC differentials for Fbxo11 Jf/+ and Mecom Jbo/+ mice compared to their respective wild-type littermates. In contrast, other studies report elevated blood neutrophils in Fbxo11 Jf/+ at P43-P44 (but not at P121-P127) ( Hardisty et al, 2003 ) and elevated blood neutrophil, macrophage, DC CD811 type, and NK cell differentials at 8 weeks ( Vikhe et al, 2020 ). The margin of neutrophil increase ( Fbxo11 Jf/+ 19.3% versus 16.6% wild-type littermates) in the latter study was smaller than the difference between males and females in inbred mouse strains ( Peters et al, 2002 ) and the percentage of neutrophils in Fbxo11 Jf/+ bulla fluid (10.3%) is actually lower than blood.…”

Section: Discussionmentioning

confidence: 80%

“…The margin of neutrophil increase ( Fbxo11 Jf/+ 19.3% versus 16.6% wild-type littermates) in the latter study was smaller than the difference between males and females in inbred mouse strains ( Peters et al, 2002 ) and the percentage of neutrophils in Fbxo11 Jf/+ bulla fluid (10.3%) is actually lower than blood. Other elevated blood myeloid classes represent small WBC populations; macrophages (<0.6%) and DC CD811 type (<3.3%) ( Vikhe et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

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Trans-cortical vessels in the mouse temporal bulla bone are a means to recruit myeloid cells in chronic otitis media and limit peripheral leukogram changes

et al. 2022

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Chronic otitis media, inflammation of the middle ear, is a sequel to acute otitis media in ∼8% of children. Chronic otitis media with effusion is the most common cause of childhood deafness and is characterised by effusion of white blood cells into the auditory bulla cavity. Skull flat bones have trans-cortical vessels which are responsible for the majority of blood flow in and out of the bone. In experimental models of stroke and aseptic meningitis there is preferential recruitment of myeloid cells (neutrophils and monocytes) from the marrow in skull flat bones. We report trans-cortical vessels in the mouse temporal bone connect to the bulla mucosal vasculature and potentially represent a means to recruit myeloid cells directly into the inflamed bulla. The mutant mouse strains Junbo (MecomJbo/+) and Jeff (Fbxo11Jf/+) develop chronic otitis spontaneously; MecomJbo/+ mice have highly cellular neutrophil (90%) rich bulla exudates whereas Fbxo11Jf/+ mice have low cellularity serous effusions (5% neutrophils) indicating differing demand for neutrophil recruitment. However we found peripheral leukograms of MecomJbo/+ and Fbxo11Jf/+ mice are similar to their respective wild-type littermate controls with healthy bullae and infer preferential mobilization of myeloid cells from temporal bulla bone marrow may mitigate the need for a systemic inflammatory reaction. The cytokines, chemokines and haematopoietic factors found in the inflamed bulla represent candidate signalling molecules for myeloid cell mobilization from temporal bone marrow. The density of white blood cells in the bulla cavity is positively correlated with extent of mucosal thickening in MecomJbo/+, Fbxo11Jf/+, and EdaTa mice and is accompanied by changes in epithelial populations and bone remodelling. In MecomJbo/+ mice there was a positive correlation between bulla cavity WBC numbers and total bacterial load. The degree of inflammation varies between contralateral bullae and between mutant mice of different ages suggesting inflammation may wax and wane and may be re-initiated by a new wave of bacterial infection. Clearance of white blood cells and inflammatory stimuli from the bulla cavity is impaired and this may create a pro-inflammatory feedback loop which further exacerbates otitis media and delays its resolution.

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Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Trans-cortical vessels in the mouse temporal bulla bone are a means to recruit myeloid cells in chronic otitis media and limit peripheral leukogram changes

et al. 2022

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“…28,29 It is a regulator of the TGF-β pathway, the Jeff mutation maps to the Fbxo11 gene, and affects FBXO11 ability to stabilize p53 leading to perturbation in the TGF-β/Smad2 signaling pathway important in immunity and inflammation. 30,31 FBXO11 has been revealed to serve as an oncogene in many types of cancers. [32][33][34] Besides, Mei et al suggested that FBXO11 was involved in CSE-induced apoptosis, inflammation and airway remodeling by NNT-AS1/miR-582-5p/FBXO11 pathway.…”

Section: Discussionmentioning

confidence: 99%

Circ-RBMS1 Knockdown Alleviates CSE-Induced Apoptosis, Inflammation and Oxidative Stress via Up-Regulating FBXO11 Through miR-197-3p in 16HBE Cells

Qiao¹,

Hu²,

Li³

et al. 2021

COPD

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Background: Emerging evidence has reported that circular RNAs (circRNAs) are aberrantly expressed and act as significant regulators in pathological processes of chronic obstructive pulmonary disease (COPD). Here, the purpose of this article was to evaluate and clarify the biological functions and mechanism of circRNA single stranded interacting protein 1 (circ-RBMS1) in cigarette smoke (CS)-induced COPD. Methods: Human bronchial epithelial cells 16HBE treated with or without cigarette smoke extract (CSE) were used in the experimental group in vitro. Levels of circ-RBMS1, microRNA (miR)-197-3p, and F-box only protein 11 (FBXO11) were detected using quantitative real-time polymerase chain reaction and Western blot. The present study used cell counting kit-8 (CCK-8), 5-ethynyl-2ʹ-deoxyuridine (EDU), flow cytometry and Western blot assays to determine the survival of 16HBE cells. The activity of interleukin (IL)-1β, tumor necrosis factor (TNF-α), malondialdehyde (MDA) and superoxide dismutase (SOD) was evaluated using the relative commercial kits. Dual-luciferase activity and RIP assays were used to identify the target relationship between miR-197-3p and circ-RBMS1 or FBXO11. Results: Circ-RBMS1 was highly expressed in COPD patients, and CSE induced an increased expression of circ-RBMS1 in a dose-dependent manner. Functionally, knockdown of circ-RBMS1 attenuated CSE-induced apoptosis, inflammation and oxidative stress in 16HBE cells. Circ-RBMS1 directly targeted miR-197-3p, and miR-197-3p inhibition reversed the effects of circ-RBMS1 knockdown on CSE-induced 16HBE cells. FBXO11 was a target of overexpression or FBXO11 silencing reduced the apoptosis, inflammation and oxidative stress in CSE-induced 16HBE cells. Moreover, miR-197-3p exerted its effects by targeting FBXO11. Additionally, circ-RBMS1 acted as a sponge for miR-197-3p to positively regulate FBXO11 expression in 16HBE cells. Conclusion: Circ-RBMS1 knockdown alleviated CSE-induced apoptosis, inflammation and oxidative stress in 16HBE cells via miR-197-3p/FBXO11 axis, suggesting a new insight into the pathogenesis of CS-induced COPD.

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“…FBXO11 promotes the degradation of proteins critical in regulation of the cell cycle, such as BCL6, SNAIL and p53. Therefore, by acting as a sponge for miR-197-3p, circ-RBMS1 positively regulates FBXO11 expression in bronchial epithelial cells, enhancing CSE-induced apoptosis, inflammation, and oxidative stress [ 109 , 110 ].…”

Section: Circular Rnasmentioning

confidence: 99%

Context-Dependent Regulation of Gene Expression by Non-Canonical Small RNAs

Plawgo

Raczyńska

2022

ncRNA

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In recent functional genomics studies, a large number of non-coding RNAs have been identified. It has become increasingly apparent that noncoding RNAs are crucial players in a wide range of cellular and physiological functions. They have been shown to modulate gene expression on different levels, including transcription, post-transcriptional processing, and translation. This review aims to highlight the diverse mechanisms of the regulation of gene expression by small noncoding RNAs in different conditions and different types of human cells. For this purpose, various cellular functions of microRNAs (miRNAs), circular RNAs (circRNAs), snoRNA-derived small RNAs (sdRNAs) and tRNA-derived fragments (tRFs) will be exemplified, with particular emphasis on the diversity of their occurrence and on the effects on gene expression in different stress conditions and diseased cell types. The synthesis and effect on gene expression of these noncoding RNAs varies in different cell types and may depend on environmental conditions such as different stresses. Moreover, noncoding RNAs play important roles in many diseases, including cancer, neurodegenerative disorders, and viral infections.

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Mutation in Fbxo11 Leads to Altered Immune Cell Content in Jeff Mouse Model of Otitis Media

Cited by 8 publications

References 35 publications

Trans-cortical vessels in the mouse temporal bulla bone are a means to recruit myeloid cells in chronic otitis media and limit peripheral leukogram changes

Trans-cortical vessels in the mouse temporal bulla bone are a means to recruit myeloid cells in chronic otitis media and limit peripheral leukogram changes

Circ-RBMS1 Knockdown Alleviates CSE-Induced Apoptosis, Inflammation and Oxidative Stress via Up-Regulating FBXO11 Through miR-197-3p in 16HBE Cells

Context-Dependent Regulation of Gene Expression by Non-Canonical Small RNAs

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