Tumor necrosis factor-alpha: a multifunctional regulator of mammary gland development.

Varela, Linda M.; Ip, Margot M.

doi:10.1210/endo.137.11.8895364

Cited by 57 publications

(29 citation statements)

References 37 publications

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“…Consistent with the constitutive mRNAexpression of proinflammatory cytokines in mammary tissues [60], the proinflammatory cytokine production here was also seen in mammary tissues obtained from sows before inoculation with E. coli. These findings are consistent with previous studies in rats, humans as well as in cows where some baseline constitutive production of cytokines takes place in normal mammary glands [7,23,56]. Similarly, proinflammatory cytokines have also been found in serum/plasma collected from healthy pregnant sows [59] as well as pregnant women [4,24,57].…”

Section: Discussionsupporting

confidence: 92%

Morphometric analysis of proinflammatory cytokines in mammary glands of sows suggests an association between clinical mastitis and local production of IL-1beta, IL-6 and TNF-alpha

et al. 2007

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-Twelve healthy primiparous sows received intramammary inoculation with Escherichia coli (serotype O127) during the 24-h period preceding parturition. Mammary gland biopsy samples were taken immediately before inoculation (0 h) and from the inoculated and the contralateral noninoculated glands 24 h after inoculation. The analyses of interleukin-1 beta (IL-1β), IL-6, IL-8, and tumor necrosis factor alpha (TNF-α) by immunohistochemistry revealed that the production of these proinflammatory cytokines significantly increased in the inoculated mammary glands of sows that developed clinical signs of mastitis (affected group, n = 4) 24 h after inoculation. This was also true for IL-8 in the inoculated mammary glands of sows that did not develop clinical signs of mastitis (nonaffected group, n = 8). Sows that developed clinical signs of mastitis displayed significantly lower constitutive production of IL-1β than did sows that remained clinically healthy. The data indicate that the development of clinical symptoms of coliform mastitis in the sow is associated with a locally increased proinflammatory cytokine production in response to intramammary E. coli infection.cytokine / immunohistochemistry / mastitis / pig / E. coli

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Section: Discussionsupporting

confidence: 92%

Morphometric analysis of proinflammatory cytokines in mammary glands of sows suggests an association between clinical mastitis and local production of IL-1beta, IL-6 and TNF-alpha

et al. 2007

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“…Consistent with previous findings 8 , analysis of HeLa-vector cells showed that IKKβ and IKKγ are detectable in a prominent pool with a relative molecular mass (M r ) of 700,000 (fractions [10][11][12] and also in a pool of ~300 K (fractions 14 and 15; Fig. 3a).…”

supporting

confidence: 91%

“…4b). Previous work has demonstrated that the effects of TNFα on mammary epithelial cells are of physiological importance for mammary gland morphogenesis during puberty and pregnancy [11][12][13][14][15] . To determine whether these effects of TNFα are regulated by MUC1, primary mouse mammary epithelial cells (MMECs) were transfected with control or mouse-specific Muc1 siRNAs (Fig.…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

MUC1 oncoprotein activates the IκB kinase β complex and constitutive NF-κB signalling

et al. 2007

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Nuclear factor-κB (NF-κB) is constitutively activated in diverse human malignancies by mechanisms that are not understood 1,2 . The MUC1 oncoprotein is aberrantly overexpressed by most human carcinomas and, similarly to NF-κB, blocks apoptosis and induces transformation [3][4][5][6] . This study demonstrates that overexpression of MUC1 in human carcinoma cells is associated with constitutive activation of NF-κB p65. We show that MUC1 interacts with the highmolecular-weight IκB kinase (IKK) complex in vivo and that the MUC1 cytoplasmic domain binds directly to IKKβ and IKKγ. Interaction of MUC1 with both IKKβ and IKKγ is necessary for IKKβ activation, resulting in phosphorylation and degradation of IκBα. Studies in non-malignant epithelial cells show that MUC1 is recruited to the TNF-R1 complex and interacts with IKKβ-IKKγ in response to TNFα stimulation. TNFα-induced recruitment of MUC1 is dependent on TRADD and TRAF2, but not the death-domain kinase RIP1. In addition, MUC1-mediated activation of IKKβ is dependent on TAK1 and TAB2. These findings indicate that MUC1 is important for physiological activation of IKKβ and that overexpression of MUC1, as found in human cancers, confers sustained induction of the IKKβ-NF-κB p65 pathway.Nuclear localization of NF-κB p65 was studied in HCT116 colon cancer and HeLa cervical cancer cells that stably express either an empty vector or MUC1 (ref. 4, also see Supplementary Information, Fig. S1a). Levels of nuclear NF-κB p65 were lower in vector cells than in cells expressing MUC1 (Fig. 1a). Human ZR-75-1 and MCF-7 breast cancer cells that express endogenous MUC1 were stably transfected to express either an empty vector or a MUC1 siRNA 4 ( Supplementary Information, Fig. S1a). Silencing of MUC1 in ZR-75-1 (ref. 4) and MCF-7 cells 7 decreased nuclear NF-κB p65 (Fig. 1b). MUC1 expression was also associated with a decrease in cytosolic NF-κB p65 levels in HeLa and ZR-75-1 cells ( Supplementary Information, Fig. S1b). To determine whether MUC1 is associated with activation of the NF-κB p65 transcription function, HeLa and ZR-75-1 cells were transfected with a construct containing a NF-κB-binding site upstream of the luciferase reporter (pNF-κB-Luc). MUC1 expression was associated with activation of pNF-κB-Luc (Fig. 1c). In contrast, MUC1 had no effect on activation of a pNF-κB-Luc construct that was mutated at the NF-κB p65 binding site (Fig. 1c). In addition, expression of Bclx L , a gene activated by NF-κB, was higher in cells expressing MUC1 (Fig. 1d). To determine whether MUC1 affects IκBα phosphorylation (as phosphorylated IκBα is targeted for ubiquitination and proteosomal degradation) cytosolic lysates were immunoblotted with an anti-phospho-IκBα antibody. Indeed, phospho-IκBα levels were significantly higher in cells expressing MUC1 (Fig. 1e). Assessment of IκBα stability indicated that MUC1 expression increases degradation of IκBα (Fig. 1f). The half-lives of IκBα in the absence and presence of MUC1, were 6.7 ± 0.5 h and 3. Fig. 2a). In vitro studies with puri...

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“…Real-time quantitative reverse transcriptase polymerase chain reaction assay for interleukin-13, interferon-c, tumour necrosis factor-a and transforming growth factor-b 1 messenger ribonucleic acid Total lung ribonucleic acid was extracted from frozen lungs using a commercial kit (ISOGEN, Nippon Gene Co., Toyama, Japan) according to the standard procedure [11]. A two-step reverse transcriptase polymerase chain reaction (RT-PCR) procedure was used according to the protocol of the TaqMan Gold RT-PCR Kit (Perkin-Elmer Applied Biosystems, Foster City, CA, USA).…”

Section: Bronchoalveolar Lavage and Cell Countingmentioning

confidence: 99%

Dissociation between airway responsiveness to methacholine and responsiveness to antigen

Kamachi

Nasuhara²,

Nishimura³

et al. 2002

Eur Respir J

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Dissociation between airway responsiveness to methacholine and responsiveness to antigen. A. Kamachi, Y. Nasuhara, M. Nishimura, T. Takahashi, Y. Homma, Y. Ohtsuka, M. Munakata. #ERS Journals Ltd 2002. ABSTRACT: Repeated aerosolized antigen challenges to brown Norway (BN) rats generate nonspecific airway hyperresponsiveness (AHR). On the other hand, some studies have demonstrated that repeated antigen challenge could attenuate antigenspecific AHR in BN rats. The authors questioned whether such dissociation in airway responses actually occurs when assessed in a single study in the same animals.The authors simultaneously measured AHR to methacholine and antigen-specific AHR in rats that were repeatedly exposed to aerosolized ovalbumin (OA) for 1 or 3 months after sensitization. Four days after the last challenge, airway responses to methacholine and OA, morphometry of the airways, the cell profile in bronchoalveolar lavage fluid, and cytokine messenger ribonucleic acid (mRNA) expression in the lungs were evaluated.The two types of AHR were modulated in opposite directions by repeated antigen challenges. The AHR to methacholine was significantly increased in the rats receiving antigen challenges compared with the control rats receiving saline challenges after sensitization; whereas, the antigen-specific AHR was significantly decreased. The number of alveolar macrophages in lavaged fluid and the expression of transforming growth factor-b 1 mRNA in lung tissue was significantly different between the antigenchallenged rats and the control rats.In conclusion, dissociation between nonspecific airway hyperresponsiveness and antigen-specific airway hyperresponsiveness in brown Norway rats after repeated antigen challenges was demonstrated. Sustained airway inflammation with macrophages and/or upregulation of transforming growth factor-b 1 messenger ribonucleic acid in the lung tissue may be responsible for this dissociation.

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Tumor necrosis factor-alpha: a multifunctional regulator of mammary gland development.

Cited by 57 publications

References 37 publications

Morphometric analysis of proinflammatory cytokines in mammary glands of sows suggests an association between clinical mastitis and local production of IL-1beta, IL-6 and TNF-alpha

Morphometric analysis of proinflammatory cytokines in mammary glands of sows suggests an association between clinical mastitis and local production of IL-1beta, IL-6 and TNF-alpha

MUC1 oncoprotein activates the IκB kinase β complex and constitutive NF-κB signalling

Dissociation between airway responsiveness to methacholine and responsiveness to antigen

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