Lactation Stage‐Dependent Changes in Levels of Tumor Necrosis Factor/Cachectin in Milk

Rewinski, Michael J.; Yang, T. J.

doi:10.1111/j.1600-0897.1994.tb00863.x

Cited by 18 publications

(12 citation statements)

References 23 publications

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“…Low concentrations of inflammatory mediators or their activity were sometimes found in milk before challenge or in the milk of uninfected glands. Although some of this activity may have been nonspecific, other investigators have also noted low concentrations of TNF, IL-6, and IL-8 in secretions of noninflamed mammary glands or unstimulated mammary epithelial cultures (5,34,46). The physiological significance of basal levels of these mediators is unknown.…”

Section: Discussionmentioning

confidence: 99%

Complement fragment C5a and inflammatory cytokines in neutrophil recruitment during intramammary infection with Escherichia coli

et al. 1997

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Generation of inflammatory mediators and leukocyte recruitment to infection at an epithelial surface were studied during Escherichia coli-induced mastitis. One uninfected gland of each of eight midlactation cows was challenged with only 30 CFU of E. coli McDonald strain 487, a serum-resistant isolate from a cow with mastitis. Bacteria grew logarithmically during the first 10 to 12 h after challenge, reaching concentrations of more than 10 5 CFU/ml with no detectable host response during this time. An intense inflammatory reaction began approximately 12 h after the challenge and was characterized by a breakdown in the blood-milk permeability barrier followed by pyrexia and a pronounced leukocytic influx. Coincident with the onset of mammary inflammation was the appearance of neutrophil chemotactic activity in the milk from infected glands. Factors able to upregulate CD18 expression on peripheral blood neutrophils also appeared in milk at this time. The lack of appearance of chemotactic and CD18-upregulating activities until 12 h after challenge indicated that delays in neutrophil recruitment resulted from an initial lack of bacterial recognition and inflammatory mediator production. Production of complement fragment C5a, tumor necrosis factor, and interleukin-1 (IL-1) occurred earlier than production of IL-6 or IL-8. The early and intense production of C5a indicates that this chemoattractant may be more important than IL-8 during the initial recruitment and activation of neutrophils to a developing E. coli infection.

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Section: Discussionmentioning

confidence: 99%

Complement fragment C5a and inflammatory cytokines in neutrophil recruitment during intramammary infection with Escherichia coli

et al. 1997

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“…Cells stimulated with Lf show several physiological functions [33,34]. On the other hand, the mRNA expression and cytokine activity of TNFα in MG cells during the dry period showed a higher level than the MG cells during the lactation period in normal cows [28]. Therefore, injection of Lfs was examined during the early dry period, while monocytes and macrophages such as target cells of Lf, in MGS increased [11,12,21].…”

Section: Inflammatory Changes Induced By Injecting the Low Con A Affimentioning

confidence: 99%

Small Molecule Lactoferrin with an Inflammatory Effect But No Apparent Antibacterial Activity in Mastitic Mammary Gland Secretion

Komine¹,

Komine²,

Kuroishi³

et al. 2005

The Journal of Veterinary Medical Science

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ABSTRACT. We have identified various lactoferrin (Lf) molecules in mastitic mammary gland secretions (MGSs), and these Lf molecules were examined for their physiological function in MG. These Lf molecules were isolated by Con A affinity chromatography, and then analyzed by various electrophoresis methods and N-terminal amino acid sequencing. The low Con A affinity Lf was found to have low molecular peptides as compared with the 86 kDa of the high Con A affinity Lf, which is usually detected in healthy MGSs. The Nterminal amino acid sequence of each of the small molecular Lfs were confirmed as fragments of 86 kDa Lf. This low Con A affinity Lf stimulated spleen adherent cells to produce more O 2 -than 86 kDa Lf. Furthermore, the low Con A affinity Lf showed low antibacterial activity against E. coli and S. aureus, and had decreased iron-binding capacity in comparison with 86 kDa Lf. Moreover, the 86 kDa Lf could stimulate bovine T cells or macrophages to produce IFN-γ, IL-4, IL-6, and IL-1α. However low Con A affinity Lf induced the production of TNFα, but not physiological T cell or macrophage cytokines. It was also found that when the healthy MGs of dry cows were injected with the low Con A affinity Lf, there was an increase in polymorphonuclear cells together with TNFα, MCP-1, and IL-8 production. These results suggested that low Con A affinity Lf in mastitic MGSs differed from 86 kDa Lf in physiological characteristics, and, that it induced an inflammatory reaction in MGs. KEY WORDS: concanavalin A, lactoferrin, mammary gland secretion, mastitis.

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“…It may be that this latter factor is more prevalent in the absence of TIMP-3, a circumstance in which TACE activity may go unchecked. During lactation and involution, mammary epithelial cells are known to express TNFR (59), and, importantly, soluble TNF-α has been found in the lumens of bovine involuting mammary glands (60). Fas-L, another member of the TNF-α superfamily, may also be more abundant in Timp-3-null tissue.…”

Section: Figurementioning

confidence: 99%

Accelerated apoptosis in the Timp-3–deficient mammary gland

Fata

Leco²,

Voura³

et al. 2001

J. Clin. Invest.

100

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IntroductionPericellular proteolysis of cell surface molecules, extracellular factors, and ECM is intrinsically linked to cell function and fate (1, 2). Regulation of these multiple proteolytic processes is primarily achieved through coordinated interactions between proteinase, their biologic inhibitors, and the substrates. Tissue inhibitors of metalloproteinases (TIMP-1 to TIMP-4) are emerging as essential regulatory molecules, given their direct inhibitory function against two metzincin families of zinc-dependent proteinases involved in pericellular proteolysis; namely, the MMPs (matrix metalloproteinases) and the ADAMs (a disintegrin and metalloprotease) (3, 4). Although considerable literature supports the involvement of TIMPs in inhibiting cell migration, invasion, angiogenesis, and metastasis, the direct influence of TIMPs on cell fate remains little explored.Although the four TIMP proteins share similar secondary and tertiary structures and in general are able to inhibit all MMPs albeit with varying degrees of affinity, TIMP-3 stands out as a unique member. For instance, unlike the other TIMPs, which after secretion become freely diffusible within the cellular microenvironment, TIMP-3 becomes tightly bound to the ECM (5-7). In addition, inherited mutations in Timp-3 lead to Sorsby fundus dystrophy, a degenerative eye disease (8). Further, Timp-3 silencing through promoter methylation is often found in cancer specimens (9, 10), whereas other TIMPs often show tumorigenic upregulation (3). TIMP-3 exhibits direct inhibitory activity against several ADAMs that are not inhibited by other TIMPs, including TNF-α convertase (TACE, ADAM-17) (11, 12), ADAM-12S (13), aggrecanase-1 (ADAM-TS4), and aggrecanase-2 (ADAM-TS5) (14). Likely through inhibition of ADAM-mediated ectodomain shedding, TIMP-3 also inhibits cell shedding of L-selectin (15) syndecans-1 and -4 (16), IL-6 receptor (17), c-MET (18), and cleavage of IGF binding proteins-3 and -5 (13). Finally, several reports have found that high levels of TIMP-3 are proapoptotic in both normal and cancer cell lines (19)(20)(21)(22)(23)(24), and that the pro-death domain resides in its N-terminal domain (25). Using mammary gland involution as a model for physiological apoptosis and recently generated TIMP-3-deficient mice The proapoptotic proteinase inhibitor TIMP-3 is the only molecule of this family thought to influence cell death. We examined epithelial apoptosis in TIMP-3-deficient mice during mammary gland involution. Lactation was not affected by the absence of TIMP-3, but glandular function, as measured by gland-to-body weight ratio and production of β-casein, was suppressed earlier during postlactational involution than in controls. Histological examination revealed accelerated lumen collapse, alveolar-epithelial loss, and adipose reconstitution in Timp-3 -/-females. Epithelial apoptosis peaked on the first day of involution in Timp-3-null glands but at day 3 in wild-type littermates. Unscheduled activation of gelatinase-A was evident by zymography and correlat...

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Lactation Stage‐Dependent Changes in Levels of Tumor Necrosis Factor/Cachectin in Milk

Abstract: These lactation stage-dependent changes in TNF alpha levels reflect differential effects that TNF alpha have on involution and prepartum remodeling of the mammary gland of the dam and on gastrointestinal development and immunoregulatory function of the suckling.

Cited by 18 publications

References 23 publications

Complement fragment C5a and inflammatory cytokines in neutrophil recruitment during intramammary infection with Escherichia coli

Complement fragment C5a and inflammatory cytokines in neutrophil recruitment during intramammary infection with Escherichia coli

Small Molecule Lactoferrin with an Inflammatory Effect But No Apparent Antibacterial Activity in Mastitic Mammary Gland Secretion

Accelerated apoptosis in the Timp-3–deficient mammary gland

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