Gas6 negatively regulates the Staphylococcus aureus‐induced inflammatory response via TLR signaling in the mouse mammary gland

Zahoor, Arshad; Yang, Ye; Yang, Chao; Akhtar, Muhammad Faheem; Guo, Yanxia; Shaukat, Aftab; Guo, Mengyao; Deng, Ganzhen

doi:10.1002/jcp.29604

Cited by 13 publications

(8 citation statements)

References 57 publications

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“…It is also worth noting that this study focussed solely on Gas6, a ligand for all three TAM receptors, and not protein S (Tsou et al, 2014;Al Kafri and Hafizi, 2019) which has also been purported to have anti-inflammatory functions (Carrera-Silva et al, 2013;Barth et al, 2018). Furthermore, we have shown here that Gas6, via the TAM receptors Axl and Mer, negatively regulates the inflammatory response downstream of multiple TLRs, and other studies are continuing to elucidate these interactions (Wu et al, 2018;Herrera-Rivero et al, 2019;Zahoor et al, 2020). It is vital to probe further to fully clarify how the TAM system is involved in pro-inflammatory cytokine mediation and the underlying signaling pathways involved.…”

Section: Gas6mentioning

confidence: 75%

Gas6 Inhibits Toll-Like Receptor-Mediated Inflammatory Pathways in Mouse Microglia via Axl and Mer

Gilchrist

Goudarzi

Hafizi

2020

Front. Cell. Neurosci.

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Background: Microglia are well known key regulators of neuroinflammation which feature in multiple neurodegenerative disorders. These cells survey the CNS and, under inflammatory conditions, become "activated" through stimulation of toll-like receptors (TLRs), resulting in changes in morphology and production and release of cytokines. In the present study, we examined the roles of the related TAM receptors, Mer and Axl, and of their ligand, Gas6, in the regulation of microglial pro-inflammatory TNF-α production and microglial morphology. Methods: Primary cultures of murine microglia of wild-type (WT), Mer −/− and Axl −/− backgrounds were stimulated by the TLR4 agonist, lipopolysaccharide (LPS) with or without pre-treatment with Gas6. Gene expression of TNF-α, Mer, and Axl was examined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA) was used to measure TNF-α release from microglia. Immunofluorescence staining of β-actin and the microglial marker Iba1 was performed to reveal microglial morphological changes, with cellular characteristics (area, perimeter, Feret's diameter, minimum Feret, roundness, and aspect ratio) being quantified using ImageJ software. Results: Under basal conditions, TNF-α gene expression was significantly lower in Axl −/− microglia compared to WT cells. However, all microglial cultures robustly responded to LPS stimulation with the upregulation of TNF-α expression to similar degrees. Furthermore, Mer receptor expression was less responsive to LPS stimulation when in Axl knockout cells. The presence of Gas6 consistently inhibited the LPS-induced upregulation of TNF-α in WT, Mer −/− and Axl −/− microglia. Moreover, Gas6 also inhibited LPS-induced changes in the microglial area, perimeter length, and cell roundness in wild-type cells.

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Section: Gas6mentioning

confidence: 75%

Gas6 Inhibits Toll-Like Receptor-Mediated Inflammatory Pathways in Mouse Microglia via Axl and Mer

Gilchrist

Goudarzi

Hafizi

2020

Front. Cell. Neurosci.

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“…8 The level of TLR2 and TLR4 protein was enhanced after macrophages infected with S. aureus, thus activating downstream NF-κB and MAPK signalling pathway and promoting the release of cytokines by macrophages. [9][10][11][12][13] S. aureus activates TLR2 receptor, and MAPK signalling pathway mediates phagocytosis and autophagy in RAW264.7 macrophage cells by upregulation of Beclin-1, LC3-II/LC3-I. 14,15 Controlling the pathological changes and protecting the tissue from damage is a usual strategy.…”

Section: Introductionmentioning

confidence: 99%

Mangiferin Inhibits Apoptosis and Autophagy Induced by Staphylococcus aureus in RAW264.7 Cells

Xu¹,

Yao²,

Wang³

et al. 2020

JIR

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Purpose Staphylococcus aureus ( S. aureus ) is an important bacterial pathogen, which creates infective inflammation to human being and animals. Mangiferin (MG) is one of the natural flavonoids with anti-inflammatory, anti-bacterial, and anti-oxidative properties. However, the anti-apoptosis and anti-autophagy of MG are unknown. Hence, this study was aimed to research the inhibition of MG on S. aureus -induced apoptosis and autophagy in RAW264.7 cells. Methods The RAW264.7 cells were pretreated with MG, or pretreated with SP600125 or anisomycin synchronously, and then infected with S. aureus (MOI=100:1). The viability and proliferation status of RAW264.7 cells were detected by MTT and EdU assay. The relative expression of TNF-α, IL-6 and IL-10 protein was tested with ELISA. The levels of Bax, Bcl-2, caspase-3, c-Jun N-terminal kinase (JNK), extracellular-regulated protein kinase (ERK), p38, LC3, Beclin-1, p62, phosphorylated JNK, phosphorylated p38 and phosphorylated ERK in cells were detected by Western blotting. The apoptosis rate of RAW264.7 cells was analyzed by flow cytometric assay. Results The study showed that MG significantly attenuated RAW264.7 cells apoptosis and autophagy caused by S. aureus . MG alleviated S. aureus -induced apoptosis by down-regulating the protein level of active caspase-3 and Bax and up-regulating the level of Bcl-2. MG also inhibited S. aureus -induced autophagy via decreasing the protein level of LC3-II/LC3-I and Beclin-1 or increasing the protein expression of p62. This protective role was dependent on the up-regulation of JNK signal pathway, which was confirmed by using JNK agonist and inhibitor. Conclusion Our results demonstrated that MG might protect RAW264.7 cells from S. aureus -induced apoptosis and autophagy via inhibiting JNK/Bax-dependent signal pathway. Therefore, MG may be a potential agent against pathological cell damage induced by S. aureus infection.

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“…Moreover, three of the overlapped genes GAS6, PKD2, and NCAM1 were previously associated with inflammation in human and mouse. Moreover, GAS6 negatively regulates the Staphylococcus aureus-induced inflammatory response in the mouse mammary gland (Zahoor et al, 2020). Staphylococcus aureus is the most prevalent contagious mastitis pathogen.…”

Section: Resultsmentioning

confidence: 99%

Genes associated with somatic cell count index in Brown Swiss cattle

Jeretina

Skok

2020

Journal of Animal Science

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Subclinical mastitis (SM) is one of the most common diseases of cows in milk production herds caused by contagious and/or environmental pathogens. Since there are no visible abnormalities in the milk or udder, detection of subclinical mastitis requires special diagnostic tests. Somatic cell count (SCC) is the most common test used to detect changes in milk due to the inflammatory process. Previously we developed somatic cell count index (SCCI), a new method for the accurate prediction of milk yield losses caused by elevated SCC. The aim of this study was to identify new candidate genetic markers for SCCI in the Slovenian population of Brown Swiss cattle (BS). For that purpose, we analyzed samples of BS cows, which were genotyped using SNP microarray ICBF International Dairy and Beef v3 (ICBF, Ireland) for a total of 53,262 single nucleotide polymorphism (SNP) markers. After quality control, the set of 18,136 SNPs were used in association analysis. Our association analysis revealed 130 SNPs associated with SCCI, which were used for haplotype and overlap analysis. Haplotypes generated from the genotyped data for those 130 SNPs revealed 10 haplotype blocks among 22 SNPs. Additionally, all 130 SNPs, mastitis related QTL, and protein-coding genes are shown on bovine genome. Overlap analysis shows that the majority of significantly associated SNPs (70) are intergenic, while 60 SNPs are mapped within, up- or downstream of the protein-coding genes. However, those genes can serve as strong candidate genes for the marker-assisted selection programs in our and possibly other populations of cattle.

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Gas6 negatively regulates the Staphylococcus aureus‐induced inflammatory response via TLR signaling in the mouse mammary gland

Cited by 13 publications

References 57 publications

Gas6 Inhibits Toll-Like Receptor-Mediated Inflammatory Pathways in Mouse Microglia via Axl and Mer

Gas6 Inhibits Toll-Like Receptor-Mediated Inflammatory Pathways in Mouse Microglia via Axl and Mer

<p>Mangiferin Inhibits Apoptosis and Autophagy Induced by <em>Staphylococcus aureus</em> in RAW264.7 Cells</p>

Genes associated with somatic cell count index in Brown Swiss cattle

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