Bacterial lipopolysaccharide induces increased expression of toll-like receptor (TLR) 4 and downstream TLR signaling molecules in bovine mammary epithelial cells

Ibeagha‐Awemu, Eveline M.; Lee, Jai-Wei; Ibeagha, Aloysius E; Bannerman, Douglas D.; Paape, Max; Zhao, Xin

doi:10.1051/vetres:2007047

Cited by 134 publications

(113 citation statements)

References 50 publications

(59 reference statements)

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“…In both studies, LPS increased TLR2, which typically recognizes bacterial lipids from gram-positive bacteria (Takeda & Akira 2005). Increased expression of TLR2 mRNA was also observed in mammary glands challenged with LPS (Ibeagha-Awemu et al 2008) as well as E. coli (Yang et al 2008). Although the reason for increased TLR2 mRNA after LPS treatment is not known, studies in mice (Matsumura et al 2000) and humans (Davanian et al 2012) suggest that LPS-induced TNF increases TLR2 mRNA and protein expression.…”

Section: Discussionmentioning

confidence: 87%

“…However, expression of both TLR2 and TLR4 mRNA increased in bovine mammary (Ibeagha-Awemu et al 2008, Ma et al 2011 and endometrial epithelial cells (Fu et al 2013) stimulated with LPS. Furthermore, these studies indicate that TLR4 is present on cells other than leukocytes.…”

Section: Introductionmentioning

confidence: 96%

“…In cows, TLR4 mRNA and protein were detected in endometrial stromal and epithelial cells by RT-PCR and flow cytometry (Herath et al 2006). Activation of TLRs by LPS was observed in endometrial (Fu et al 2013) as well as in mammary epithelial cells (Ibeagha-Awemu et al 2008), thus inducing the downstream signaling cascade that culminates in the secretion of proinflammatory cytokines. In bovine granulosa cells, TLR4 was detected and an inflammatory response to LPS was observed and linked to reduced fertility, due to reduced follicular steroidogenesis .…”

Section: Introductionmentioning

confidence: 99%

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LPS-mediated effects and spatio-temporal expression of TLR2 and TLR4 in the bovine corpus luteum

Lüttgenau¹,

Herzog²,

Strüve³

et al. 2016

Reproduction

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When given intravenously (iv), lipopolysaccharide (LPS) transiently suppresses the structure and function of the bovine corpus luteum (CL). This is associated with increased release of prostaglandin (PG) F 2a metabolite. The underlying regulatory mechanisms of this process remain, however, obscure. Therefore, the aims of this study were: i) to investigate the expression of the LPS receptor toll-like receptor 4 (TLR4) and 2 (TLR2) in the bovine CL during early, mid-and late luteal phases; and ii) to further dissect the mechanisms of LPS-mediated suppression of luteal function. As revealed by semi-quantitative qPCR and immunohistochemistry, both receptors were detectable throughout the luteal lifespan. Their mRNA levels increased from the early toward the mid-luteal phase; no further changes were observed thereafter. The TLR4 protein seemed more highly represented than TLR2. The cellular localization of TLRs was in blood vessels; weaker signals were observed in luteal cells. Additionally, cows were treated either with LPS (iv, 0.5 mg/kg BW) or with saline on Day 10 after ovulation. Samples were collected 1200 h after treatment and on Day 10 of the respective subsequent (untreated) cycle. The mRNA expression of several possible regulatory factors was investigated, revealing the suppression of PGF 2a receptor (PTGFR), STAR protein and 3b-hydroxysteroid dehydrogenase, compared with controls and subsequent cycles. The expression of TLR2 and TLR4, interleukin 1a (IL1A) and 1b (IL1B) and of PGF 2a and PGE 2 synthases (HSD20A and mPTGES respectively) was increased. The results demonstrate the presence of TLR2 and TLR4 in the bovine CL, and implicate their possible involvement in the deleterious effects of LPS on its function.

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Section: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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LPS-mediated effects and spatio-temporal expression of TLR2 and TLR4 in the bovine corpus luteum

Lüttgenau¹,

Herzog²,

Strüve³

et al. 2016

Reproduction

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“…The recognition of LTA by leucocytes requires TLR2 and is improved by interaction with CD14 [45]. Bovine mammary tissue and bovine MEC express transcripts of the gene coding TLR2 [16,51], and the protein is expressed on bovine MEC [24]. Bovine MEC express transcripts for CD14 [51], and the protein is found on the milk fat globule membrane [42], which derives from the apical face of MEC.…”

Section: Discussionmentioning

confidence: 99%

“…Each one received at time zero RPMI in one quarter, 10 g LTA in another one, and 100 g LTA in a third quarter. The infused quarters were aseptically sampled just before infusion after the morning milking, then 4,8,12,16,24,32,48,72 and 96 h post-infusion. At each sampling time up to 24 h post-infusion, the rectal temperature was taken and a clinical examination was performed (appearance of gland and milk).…”

Section: Experimental Designmentioning

confidence: 99%

Staphylococcus aureuslipoteichoic acid triggers inflammation in the lactating bovine mammary gland

et al. 2008

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-The response of the bovine mammary gland to lipoteichoic acid (LTA), which is a major pathogen-associated molecular pattern of Gram-positive bacteria, was investigated by infusing purified Staphylococcus aureus LTA in the lumen of the gland. LTA was able to induce clinical mastitis at the dose of 100 g/quarter, and a subclinical inflammatory response at 10 g/quarter. The induced inflammation was characterized by a prompt and massive influx of neutrophils in milk. LTA proved to induce strongly the secretion of the chemokines CXCL1, CXCL2, CXCL3 and CXCL8, which target mainly neutrophils. The complement-derived chemoattractant C5a was generated in milk only with the highest dose of LTA (100 g). The pro-inflammatory cytokine IL-1 was induced in milk, but there was very little if any TNF-and no IFN-. The re-assessment of CXCL8 concentrations in milk whey of quarters previously challenged with S. aureus, by using an ELISA designed for bovine CXCL8, showed that this chemokine was induced in milk, contradicting previous reports. Overall, S. aureus LTA elicited mammary inflammatory responses that shared several attributes with S. aureus mastitis. Purified LTA looks promising as a convenient tool to investigate the inflammatory and immune responses of the mammary gland to S. aureus. Staphylococcus aureus / mastitis / cattle / lipoteichoic acid / chemokine

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Bifunctional role of ephrin A1‐Eph system in stimulating cell proliferation and protecting cells from cell death through the attenuation of ER stress and inflammatory responses in bovine mammary epithelial cells

Kang

Jeong

Bae

et al. 2017

Journal Cellular Physiology

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Structural and functional development of the mammary gland is constant in the mammary gland life cycle. Eph receptors and their ligands, ephrins, control events through cell-to-cell interactions during embryonic development, and adult tissue homeostasis; however, little information on participation of ephrin A1, a representative ligand of the Eph receptor, in the development and function of normal mammary glands is known. In this study, we demonstrated functional effects of the ephrin A1-Eph system and mechanisms of its action on bovine mammary epithelial (MAC-T) cells. The in vitro cultured MAC-T cells expressed the ephrin A1 ligand and EphA1, A2, A4, A7, and A8 among the eight members of the Eph A family. Our results revealed that ephrin A1 induced MAC-T cell cycle progression and stimulated cell proliferation with abundant expression of nucleic PCNA and cyclin D1 proteins. Additionally, ephrin A1 induced activation of intracellular signaling molecules involved in PI3 K/AKT and MAPK signaling, and the proliferation-stimulating effect of ephrin A1 was mediated by activation of these pathways. Furthermore, ephrin A1 influenced expression and activation of various ER stress-related proteins and protected MAC-T cells from stress-induced cell death. Finally, ephrin A1 alleviated LPS-induced cell death through down-regulation of inflammatory cytokines. In conclusion, the results of this study suggest that the Eph A-ephrin A1 system is a positive factor in the increase and maintenance of epithelial cells in mammary glands of cows; the signaling system contributes to development, remodeling, and functionality of normal mammary glands and could overcome mastitis in cows and other mammals.

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Bacterial lipopolysaccharide induces increased expression of toll-like receptor (TLR) 4 and downstream TLR signaling molecules in bovine mammary epithelial cells

Cited by 134 publications

References 50 publications

LPS-mediated effects and spatio-temporal expression of TLR2 and TLR4 in the bovine corpus luteum

LPS-mediated effects and spatio-temporal expression of TLR2 and TLR4 in the bovine corpus luteum

Staphylococcus aureuslipoteichoic acid triggers inflammation in the lactating bovine mammary gland

Bifunctional role of ephrin A1‐Eph system in stimulating cell proliferation and protecting cells from cell death through the attenuation of ER stress and inflammatory responses in bovine mammary epithelial cells

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