IL‐1/IL‐1R signaling induced by all‐<i>trans</i>‐retinal contributes to complement alternative pathway activation in retinal pigment epithelium

Cheng, Xin; He, Danxue; Liao, Chunyan; Lin, Sijie; Tang, Liying; Wang, Yuanliang; Hu, Jiaoyue; Li, Wei; Liu, Zuguo; Wu, Yalin; Liao, Yi

doi:10.1002/jcp.30103

Cited by 8 publications

(4 citation statements)

References 52 publications

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“…To further investigate if the immune response in the Fmr1 KO is different than in wild types, we assessed the correlations between the expression of cytokines and the complement system target C3. The cytokines IL-6, IL-1β, and TNF-α have been previously shown to modulate C3 signaling [32,45]. In wild-type mice, we found a correlation between IL-6 and C3 at baseline, while, after LPS administration, C3 expression presented a positive correlation with the expression of IL-1β and TNF-α.…”

Section: Discussionsupporting

confidence: 46%

Hippocampal Upregulation of Complement Component C3 in Response to Lipopolysaccharide Stimuli in a Model of Fragile-X Syndrome

Santana-Coelho,

Lugo

2023

CIMB

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The complement system is part of the innate immune system and has been shown to be altered in autism spectrum disorder (ASD). Fragile-X syndrome (FXS) is the main genetic cause of ASD and studies suggest a dysregulation in the immune system in patients with the disorder. To assess if an animal model of FXS presents with altered complement signaling, we treated male Fmr1 knockout (KO) mice with lipopolysaccharide (LPS) and collected the hippocampus 24 h later. Assessment of the expression of the complement genes C1q, C3, and C4 identified the upregulation of C3 in both wild-type (WT) and knockout mice. Levels of C3 also increased in both genotypes. Analysis of the correlation between the expression of C3 and the cytokines IL-6, IL-1β, and TNF-α identified a different relationship between the expression of the genes in Fmr1 KO when compared to WT mice. Our findings did not support our initial hypotheses that the lack of the FMR1 gene would alter complement system signaling, and that the induction of the complement system in response to LPS in Fmr1 KO mice differed from wild-type conspecifics.

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Section: Discussionsupporting

confidence: 46%

Hippocampal Upregulation of Complement Component C3 in Response to Lipopolysaccharide Stimuli in a Model of Fragile-X Syndrome

Santana-Coelho,

Lugo

2023

CIMB

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“…We found that IL-1β could signi cantly promote the expression of CFH in FLSs and healthy controls-derived monocytes. IL-1/IL-1R signaling induced by all-trans-retinal contributes to complement alternative pathway activation in retinal pigment epithelium 29 .…”

Section: Discussionmentioning

confidence: 99%

Complement Factor H attenuates TNF-α-induced inflammation by upregulating EIF3C in rheumatoid arthritis

Jia,

Feng,

et al. 2023

Preprint

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Objective To explore the role and underlying mechanism of Complement Factor H (CFH) in the peripheral and joint inflammation of RA patients. Methods The levels of CFH in the serum and synovial fluid were determined by ELISA. The pyroptosis of monocytes was determined by western blotting. The inflammation cytokine release was tested by ELISA. The cell migration and invasion ability of fibroblast-like synoviocyte (FLS) were tested by Wound healing Assay and transwell assay, respectively. The potential target of CFH was identified by RNA sequencing. Results CFH levels were significantly elevated in the serum and synovial fluid from RA and associated with high sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), and disease activity score 28 (DAS28). TNF-α could inhibit CFH expression, and CFH combined with TNF-α significantly decreased cleaved-caspase 3, gasdermin E N-terminal (GSDME-N), and inflammatory cytokines release (IL-1β and IL-6) of RA-derived monocytes. Stimulated with TNF-α increased CFH levels in RA FLS and CFH inhibits the migration, invasion and TNF-α–induced production of inflammatory mediators, including proinflammatory cytokines (IL-6, IL-8) as well as matrix metalloproteinases (MMPs, MMP1 and MMP3) of RA FLSs. The RNA-seq results showed that CFH treatment induced upregulation of eukaryotic translation initiation factor 3 (EIF3C) and the migration of RA FLSs was promoted and the expressions of IL-6, IL-8, and MMP-3 were enhanced upon EIF3C knockdown under the stimulation of CFH combined with TNF-α. Conclusion In conclusion, we have unfolded the anti-inflammatory roles of CFH in the peripheral and joints of RA, which might provide a potential therapeutic target for RA patients.

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“…The complement system is widely expressed in central and peripheral nerves. Complement signaling has been associated with several neurological disorders, including traumatic brain injury, age-related macular degeneration, and Alzheimer's disease (63)(64)(65)(66)(67)(68). While most studies focus on the impact of the classical complement pathway, the role of alternative complement signaling in neuronal dysfunction and disorder remains to be explored.…”

Section: Discussionmentioning

confidence: 99%

Complement factor B is essential for the proper function of the peripheral auditory system

et al. 2023

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Sensorineural hearing loss is associated with dysfunction of cochlear cells. Although immune cells play a critical role in maintaining the inner ear microenvironment, the precise immune-related molecular mechanisms underlying the pathophysiology of hearing loss remain unclear. The complement cascade contributes to the regulation of immune cell activity. Additionally, activation of the complement cascade can lead to the cellular opsonization of cells and pathogens, resulting in their engulfment and elimination by phagocytes. Complement factor B (fB) is an essential activator protein in the alternative complement pathway, and variations in the fB gene are associated with age-related macular degeneration. Here we show that mice of both sexes deficient in fB functional alleles (fB−/−) demonstrate progressive hearing impairment. Transcriptomic analysis of auditory nerves from adult mice detected 706 genes that were significantly differentially expressed between fB−/− and wild-type control animals, including genes related to the extracellular matrix and neural development processes. Additionally, a subset of differentially expressed genes was related to myelin function and neural crest development. Histological and immunohistochemical investigations revealed pathological alterations in auditory nerve myelin sheathes of fB−/− mice. Pathological alterations were also seen in the stria vascularis of the cochlear lateral wall in these mice. Our results implicate fB as an integral regulator of myelin maintenance and stria vascularis integrity, underscoring the importance of understanding the involvement of immune signaling pathways in sensorineural hearing loss.

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IL‐1/IL‐1R signaling induced by all‐trans‐retinal contributes to complement alternative pathway activation in retinal pigment epithelium

Cited by 8 publications

References 52 publications

Hippocampal Upregulation of Complement Component C3 in Response to Lipopolysaccharide Stimuli in a Model of Fragile-X Syndrome

Hippocampal Upregulation of Complement Component C3 in Response to Lipopolysaccharide Stimuli in a Model of Fragile-X Syndrome

Complement Factor H attenuates TNF-α-induced inflammation by upregulating EIF3C in rheumatoid arthritis

Complement factor B is essential for the proper function of the peripheral auditory system

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