UFL1 modulates NLRP3 inflammasome activation and protects against pyroptosis in LPS-stimulated bovine mammary epithelial cells

Li, Chengmin; Wang, Xinling; Kuang, Meiqian; Li, Lian; Wang, Yiru; Yang, Fang; Wang, Genlin

doi:10.1016/j.molimm.2019.04.023

Cited by 31 publications

(18 citation statements)

References 43 publications

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“…interactions in Bladder Epithelial Cells (Demirel et al, 2018) and BMECs (Li et al, 2019). In the present study, we found that NLRP3 gene was upregulated at both transcript and protein levels, and knockdown of NLRP3 expression inhibited the expression of pro-caspase-1, IL-1β, and PTGS (COX-2).…”

supporting

confidence: 51%

“…The activation of caspase-1 is responsible for the secretion of the mature IL-1β (Guo et al ., 2015; Ozaki, et al ., 2015; Jo et al ., 2016). NLRP3 was not only important for the assembly of the inflammasome and maturation of IL-1β, but also caused cellular changes that affected host-bacteria interactions in Bladder Epithelial Cells (Demirel et al ., 2018) and BMECs (Li et al ., 2019). In the present study, we found that NLRP3 gene was upregulated at both transcript and protein levels, and knockdown of NLRP3 expression inhibited the expression of pro-caspase-1, IL-1β, and PTGS (COX-2).…”

Section: Discussionmentioning

confidence: 99%

“…Although some studies have investigated the activation of LPS-induced Toll-like receptor 4 (TLR4) and NF-κB and the production of secreted cytokines IL-1β and IL-6 in BMECs (Günther et al ., 2016; Wang et al ., 2018), the NOD-like receptor (NLR) pathways involved in regulating the secretion of mature IL-1β in E. coli mastitis has not yet been characterized. The procession and secretion of mature IL-1β is required for the activation of NACHT, LRR and PYD domain-containing protein 3 (NLRP3) inflammasome (Wang et al ., 2014; Lemarchand et al ., 2019), and this NLRP3 inflammasome plays an important role in the development of LPS-induced mastitis (Li et al ., 2019).…”

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confidence: 99%

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Gene microarray integrated with iTRAQ-based proteomics for the discovery of NLRP3 in LPS-induced inflammatory response of bovine mammary epithelial cells

Sun

et al. 2019

Journal of Dairy Research

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Mastitis, a major infectious disease in dairy cows, is characterized by an inflammatory response to pathogens such as Escherichia coli and Staphylococcus aureus. To better understand the immune and inflammatory response of the mammary gland, we stimulated bovine mammary gland epithelial cells (BMECs) with E. coli-derived lipopolysaccharide (LPS). Using transcriptomic and proteomic analyses, we identified 1019 differentially expressed genes (DEGs, fold change ≥2 and P-value < 0.05) and 340 differentially expressed proteins (DEPs, fold change ≥1.3 and P-value < 0.05), of which 536 genes and 162 proteins were upregulated and 483 genes and 178 proteins were downregulated following exposure to LPS. These differentially expressed genes were associated with 172 biological processes; 15 Gene Ontology terms associated with response to stimulus, 4 associated with immune processes, and 3 associated with inflammatory processes. The DEPs were associated with 51 biological processes; 2 Gene Ontology terms associated with response to stimulus, 1 associated with immune processes, and 2 associated with inflammatory processes. Meanwhile, several pathways involved in mammary inflammation, such as Toll-like receptor, NF-κB, and NOD-like receptor signaling pathways were also represented. NLRP3 depletion significantly inhibited the expression of IL-1β and PTGS2 by blocking caspase-1 activity in LPS-induced BMECs. These results suggest that NLR signaling pathways works in coordination with TLR4/NF-κB signaling pathways via NLRP3-inflammasome activation and pro-inflammatory cytokine secretion in LPS-induced mastitis. The study highlights the function of NLRP3 in an inflammatory microenvironment, making NLRP3 a promising therapeutic target in Escherichia coli mastitis.

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supporting

confidence: 51%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Gene microarray integrated with iTRAQ-based proteomics for the discovery of NLRP3 in LPS-induced inflammatory response of bovine mammary epithelial cells

Sun

et al. 2019

Journal of Dairy Research

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“…The construction of mastitis model of cows was frequently based on 1 μg/mL LPS stimulation for BMECs in vitro in many studies [ 33 , 34 , 35 , 36 , 37 ]. There were some studies which reported that a lower concentration of LPS, such as 0.1 [ 38 , 39 ], 0.2 [ 40 , 41 ], 0.5 [ 42 ] μg/mL and so on, could also induce inflammatory responses of BMECs. In the present study, 0.01 μg/mL LPS only significantly promoted the gene expression of IL-6 and IL-8 .…”

Section: Discussionmentioning

confidence: 99%

Effects of Peptidoglycan, Lipoteichoic Acid and Lipopolysaccharide on Inflammation, Proliferation and Milk Fat Synthesis in Bovine Mammary Epithelial Cells

Sun

Zhu

et al. 2020

Toxins

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The mammary gland of the cow is particularly susceptible to infections of a wide range of pathogenic bacteria, including both Gram-positive and Gram-negative bacteria. The endotoxins of these pathogenic bacteria include peptidoglycan (PGN), lipoteichoic acid (LTA) and lipopolysaccharide (LPS), and they are the pathogen-associated molecular patterns (PAMPs) to induce mastitis. LPS can directly inhibit proliferation and milk fat synthesis of bovine mammary epithelial cells (BMECs) while inducing mastitis, but it is unclear whether PGN and LTA also have such effects. Furthermore, since the three PAMPs usually appear simultaneously in the udder of cows with mastitis, their synergistic effects on proliferation and milk fat synthesis of BMECs are worth investigating. The immortalized BMECs (MAC-T cells) were stimulated for 24 h using various concentrations of PGN, LTA and LPS, respectively, to determine the doses that could effectively cause inflammatory responses. Next, the cells were stimulated for 24 h with no endotoxins (CON), PGN, LTA, LPS, PGN + LTA, and PGN + LTA + LPS, respectively, with the predetermined doses to analyze their effects on proliferation and milk fat synthesis of BMECs. PGN, LTA and LPS successfully induced inflammatory responses of BMECs with doses of 30, 30 and 0.1 μg/mL, respectively. Although the proliferation of BMECs was significantly inhibited in the following order: LTA < PGN + LTA < PGN + LTA + LPS, there was no change in cell morphology and cell death. LTA significantly promoted the expression of fatty acid synthesis-related genes but did not change the content of intracellular triglyceride (TG), compared with the CON group. The mRNA expression of fatty acid synthesis-related genes in the LPS group was the lowest among all the groups. Meanwhile, LPS significantly decreased the content of intracellular non-esterified fatty acids (NEFAs) and TG, compared with the CON group. PGN had no effects on milk fat synthesis. Co-stimulation with PGN, LTA and LPS significantly increased the expression of fat acid synthesis-related genes and the intracellular NEFAs, but decreased intracellular TG, compared with sole LPS stimulation. Collectively, PGN, LTA and LPS showed an additive effect on inhibiting proliferation of BMECs. The promoting role of LTA in fatty acid synthesis might offset the negative effects of LPS in this regard, but co-stimulation with PGN, LTA and LPS significantly decreased intracellular TG content.

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“…Inflammasome activation is generally considered beneficial for bacterial clearance; however, exacerbating activation of inflammasomes may cause serious side effects [ 12 ]. Previous studies have shown that inflammation and cell damage are critical in BM pathogenesis [ 13 ], but attenuation of ASC-independent NLRP3 inflammasome activation, on the other hand, significantly ameliorates BM severity [ 14 ]. Therefore, targeting inflammasome activity should be a potential solution in treating BM.…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial Effect of Zophobas morio Hemolymph against Bovine Mastitis Pathogens

Liu

et al. 2020

Microorganisms

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Coliforms and Staphylococcus spp. infections are the leading causes of bovine mastitis. Despite extensive research and development in antibiotics, they have remained inadequately effective in treating bovine mastitis induced by multiple pathogen infection. In the present study, we showed the protective effect of Zophobas morio (Z. morio) hemolymph on bovine mammary epithelial cells against bacterial infection. Z. morio hemolymph directly kills both Gram-positive and Gram-negative bacteria through membrane permeation and prevents the adhesion of E. coli or the clinically isolated S. simulans strain to bovine mammary epithelial (MAC-T) cells. In addition, Z. morio hemolymph downregulates the expression of nucleotide-binding oligomerization domain (NOD)-like receptor family member pyrin domain-containing protein 3 (NLRP3), caspase-1, and NLRP6, as well as inhibits the secretion of interleukin-1β (IL-1β) and IL-18, which attenuates E. coli or S. simulans-induced pyroptosis. Overall, our results suggest the potential role of Z. morio hemolymph as a novel therapeutic candidate for bovine mastitis.

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UFL1 modulates NLRP3 inflammasome activation and protects against pyroptosis in LPS-stimulated bovine mammary epithelial cells

Cited by 31 publications

References 43 publications

Gene microarray integrated with iTRAQ-based proteomics for the discovery of NLRP3 in LPS-induced inflammatory response of bovine mammary epithelial cells

Gene microarray integrated with iTRAQ-based proteomics for the discovery of NLRP3 in LPS-induced inflammatory response of bovine mammary epithelial cells

Effects of Peptidoglycan, Lipoteichoic Acid and Lipopolysaccharide on Inflammation, Proliferation and Milk Fat Synthesis in Bovine Mammary Epithelial Cells

Antimicrobial Effect of Zophobas morio Hemolymph against Bovine Mastitis Pathogens

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