LPS induces pro-inflammatory response in mastitis mice and mammary epithelial cells: Possible involvement of NF-κB signaling and OPN

Xiao, Hong-Bo; Wang, C.-R.; Liu, Z.-K.; Wang, J.-Y.

doi:10.1016/j.patbio.2014.10.005

Cited by 20 publications

(15 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These actions that resolve the infections are not without costs as the tight junctions of MECs loosen as a result of proinflammatory signaling and PMN diapedesis [12,13]. Some of the MECs undergo apoptosis because of these stresses which induce caspase 3 expression or activation [14,15]. Because of the dramatic increase in PMN number recruited into the infected areas, we hypothesized that mastitis may cause localized hypoxia due to increased oxygen consumption by these cells.…”

Section: Introductionmentioning

confidence: 99%

Bacterial Endotoxin Induces Oxidative Stress and Reduces Milk Protein Expression and Hypoxia in the Mouse Mammary Gland

Spitzer

Tian

Choudhary

et al. 2020

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

The aim of this study was to investigate the mechanisms underlying the reduced milk production during mastitis. We hypothesized that bacterial endotoxin induces hypoxia, oxidative stress, and cell apoptosis while inhibiting milk gene expression in the mammary gland. To test this hypothesis, the left and right sides of the 4th pair of mouse mammary glands were alternatively injected with either lipopolysaccharide (LPS, E. coli 055: B5, 100 μL of 0.2 mg/mL) or sterile PBS through the teat meatus 3 days postpartum. At 10.5 and 22.5 h postinjection, pimonidazole HCl, a hypoxyprobe, was injected intraperitoneally. At 12 or 24 h after the LPS injection, the 4th glands were individually collected (n=8) and analyzed. LPS treatment induced mammary inflammation at both 12 and 24 h but promoted cell apoptosis only at 12 h. Consistently, H2O2 content was increased at 12 h (P<0.01), but dropped dramatically at 24 h (P<0.01) in the LPS-treated gland. Nevertheless, the total antioxidative capacity in tissue tended to be decreased by LPS at both 12 and 24 h (P=0.07 and 0.06, respectively). In agreement with these findings, LPS increased or tended to increase the mRNA expression of antioxidative genes Nqo1 at 12 h (P=0.05) and SLC7A11 at 24 h (P=0.08). In addition, LPS inhibited mammary expression of Csn2 and Lalba across time and protein expression of Csn1s1 at 24 h (P<0.05). Furthermore, hypoxyprobe staining intensity was greater in the alveoli of the PBS-treated gland than the LPS-treated gland at both 12 and 24 h, demonstrating a rise in oxygen tension by LPS treatment. In summary, our observations indicated that while intramammary LPS challenge incurs inflammation, it induces oxidative stress, increases cell apoptosis and oxygen tension, and differentially inhibits the milk protein expression in the mammary gland.

show abstract

Section: Introductionmentioning

confidence: 99%

Bacterial Endotoxin Induces Oxidative Stress and Reduces Milk Protein Expression and Hypoxia in the Mouse Mammary Gland

Spitzer

Tian

Choudhary

et al. 2020

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

show abstract

“…Mammary epithelial and macrophage responses, relevant during mastitis (Lam et al, 2009;Xiao et al, 2015), were modeled using the murine mammary epithelial cell line (HC11), a prolactin responsive clone COMMA-1D derived from mammary tissue of BALB/c mice in mis-pregnancy (Katz and Streuli, 2007); and a murine phagocytic monocyte J774A.1 (ATCC R TIB-67 TM ) derived from BALB/c mice, conventionally used as a macrophage model. To assess the role of exogenous cathelicidin in protothecosis, murine macrophages and mammary epithelial cells were challenged with P. bovis (1 × 10 5 CFU/mL resuspended in DMEM/F12) ± synthetic human cathelicidin LL-37 amide (H-Leu-Leu-Gly-Asp-Phe-Phe-Arg-Lys-Ser-Lys-Glu-Lys-Ile-Gly-Lys-Glu-Phe-Lys-Arg-Ile-Val-Gln-Arg-Ile-Lys-Asp-Phe-Leu-Arg-Asn-Leu-Val-Pro-Arg-Thr-Glu-Ser-NH2 trifluoroacetate salt) (10 µg/mL; H-6224; Bachem) for up to 8 h (37 • C with 5% CO 2 ).…”

Section: P Bovis Infection In Cultured Murine Bone Marrow-derived Mamentioning

confidence: 99%

Murine and Human Cathelicidins Contribute Differently to Hallmarks of Mastitis Induced by Pathogenic Prototheca bovis Algae

Shahid

Cavalcante

Knight

et al. 2020

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Prototheca bovis (formerly P. zopfii genotype-II) is an opportunistic, achlorophyllous alga that causes mastitis in cows and skin disease in cats and dogs, as well as cutaneous lesions in both immunocompetent and immunosuppressed humans. Antifungal medications are commonly ineffective. This study aimed to investigate innate immune responses contributed by cathelicidins to P. bovis in the mammary gland using a mastitis model in mice deficient in the sole murine cathelicidin (Camp). We determined P. bovis caused acute mastitis in mice and induced Camp gene transcription. Whereas, Camp −/− and Camp +/+ littermates had similar local algae burden, Camp +/+ mice produced more pro-inflammatory cytokines, TNF-α, and Cxcl-1. Likewise, Camp +/+ bone marrow-derived macrophages were more responsive to P. bovis, producing more TNF-α and Cxcl-1. Human cathelicidin (LL-37) exhibited a different effect against P. bovis; it had direct algicidal activity against P. bovis and lowered TNF-α, Cxcl-1, and IL-1β production in both cultured murine macrophages and mammary epithelial cells exposed to the pathogenic algae. In conclusion, cathelicidins were involved in protothecosis pathogenesis, with unique roles among the diverse peptide family. Whereas, endogenous cathelicidin (Camp) was key in mammary gland innate defense against P. bovis, human LL-37 had algicidal and immunomodulatory functions.

show abstract

“…Inflammation‐induced NFκB activation in immune cells has been associated with cancer pathogenesis and maintenance of a proinflammatory environment in the tumor niche . The role of NFκB in the inflammation‐dictated cells toward maintaining a proinflammatory/survival condition by activating the expression of proinflammatory cytokines such as IL‐6, IL‐1β and prosurvival proteins such as Bcl2 has been a talking point for many years now …”

Section: Introductionmentioning

confidence: 99%

“…11,12 The role of NFjB in the inflammation-dictated cells toward maintaining a proinflammatory/survival condition by activating the expression of proinflammatory cytokines such as IL-6, IL-1b and prosurvival proteins such as Bcl2 has been a talking point for many years now. 13,14 The symbiotic relationship between inflammation and cancer is supported by recent findings that indicate a reciprocal interaction between NFjB and p53, the major transcription factors known to regulate inflammation and tumor suppression, respectively. 15 This antagonistic relationship modulates the regulatory cascades that finally dictate the intracellular stress signals and initiate a proliferative cue for tumor formation.…”

Section: Introductionmentioning

confidence: 99%

Fluoxetine triggers selective apoptosis in inflammation‐induced proliferating (Ki‐67^high) thymocytes

et al. 2019

View full text Add to dashboard Cite

Inappropriate functioning of the immune system is observed during sustained systemic inflammation, which might lead to immune deficiencies, autoimmune disorders and cancer. Primary lymphoid organs may progress to a deregulated proliferative state in response to inflammatory signals in order to intensify host defense mechanisms and exacerbate an inflammatory niche. Fluoxetine, a selective serotonin reuptake inhibitor, has recently been projected as an anti‐inflammatory agent. This study had been designed to evaluate the potential novel role of fluoxetine in reversing inflammation‐induced immune dysfunction. Lipopolysaccharide (LPS) administration in Swiss albino mice potentiated a systemic inflammatory response, along with increased proliferation of thymocytes and peripheral blood mononuclear cells, as evident from increased Ki‐67 expression. The proliferative changes in the immune system were mainly associated with increased phosphorylation of PI3k, AKT and IκB along with elevated NFκB‐p65 nuclear translocation. The Ki‐67high thymocytes obtained from LPS administered mice demonstrated significantly low p53 nuclear activity, which was established to be mediated by NFκB through reduced nuclear translocation of p53 during LPS‐induced proliferative conditions, thereby blocking p53‐dependent apoptosis. Fluoxetine supplementation not only reversed the proinflammatory condition, but also induced selective apoptosis in the proliferation‐dictated Ki‐67high thymocytes possibly by modulating the hypothalamus–pituitary–adrenal axis and inducing glucocorticoid receptor activation and apoptosis in these proliferation‐biased immune cells, authenticating a novel antiproliferative role of an established drug.

show abstract

LPS induces pro-inflammatory response in mastitis mice and mammary epithelial cells: Possible involvement of NF-κB signaling and OPN

Cited by 20 publications

References 28 publications

Bacterial Endotoxin Induces Oxidative Stress and Reduces Milk Protein Expression and Hypoxia in the Mouse Mammary Gland

Bacterial Endotoxin Induces Oxidative Stress and Reduces Milk Protein Expression and Hypoxia in the Mouse Mammary Gland

Murine and Human Cathelicidins Contribute Differently to Hallmarks of Mastitis Induced by Pathogenic Prototheca bovis Algae

Fluoxetine triggers selective apoptosis in inflammation‐induced proliferating (Ki‐67^high) thymocytes

Contact Info

Product

Resources

About

LPS induces pro-inflammatory response in mastitis mice and mammary epithelial cells: Possible involvement of NF-κB signaling and OPN

Cited by 20 publications

References 28 publications

Bacterial Endotoxin Induces Oxidative Stress and Reduces Milk Protein Expression and Hypoxia in the Mouse Mammary Gland

Bacterial Endotoxin Induces Oxidative Stress and Reduces Milk Protein Expression and Hypoxia in the Mouse Mammary Gland

Murine and Human Cathelicidins Contribute Differently to Hallmarks of Mastitis Induced by Pathogenic Prototheca bovis Algae

Fluoxetine triggers selective apoptosis in inflammation‐induced proliferating (Ki‐67high) thymocytes

Contact Info

Product

Resources

About

Fluoxetine triggers selective apoptosis in inflammation‐induced proliferating (Ki‐67^high) thymocytes