Inflammatory and Anti-inflammatory Cytokines Regulate the Recovery from Sublethal X Irradiation in Rat Thymus

Mizutani, Noriko; Fujikura, Yoshihisa; Wang, Yu-Hsueh; Tamechika, Masakatsu; Tokuda, Nobuko; Sawada, Teruo; Fukumoto, Tetsuo

doi:10.1667/0033-7587(2002)157[0281:iaaicr]2.0.co;2

Cited by 23 publications

(19 citation statements)

References 37 publications

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“…As already described for irradiated rat thymus, early induction of IL-1␤ and IL-6 expression was associated with myeloid cell recruitment and activation (31). In Vanin-1 Ϫ/Ϫ mice, the higher reconstitution rate following irradiation is correlated with reduced inflammation.…”

Section: Discussionsupporting

confidence: 69%

Vanin-1^−/− Mice Exhibit a Glutathione-Mediated Tissue Resistance to Oxidative Stress

Berruyer-Pouyet

Martin

Castellano

et al. 2004

Molecular and Cellular Biology

162

161

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Vanin-1 is an epithelial ectoenzyme with pantetheinase activity and generating the amino-thiol cysteamine through the metabolism of pantothenic acid (vitamin B 5 ). Here we show that Vanin-1 ؊/؊ mice, which lack cysteamine in tissues, exhibit resistance to oxidative injury induced by whole-body ␥-irradiation or paraquat. This protection is correlated with reduced apoptosis and inflammation and is reversed by treating mutant animals with cystamine. The better tolerance of the Vanin-1 ؊/؊ mice is associated with an enhanced gammaglutamylcysteine synthetase activity in liver, probably due to the absence of cysteamine and leading to elevated stores of glutathione (GSH), the most potent cellular antioxidant. Consequently, Vanin-1 ؊/؊ mice maintain a more reducing environment in tissue after exposure to irradiation. In normal mice, we found a stress-induced biphasic expression of Vanin-1 regulated via antioxidant response elements in its promoter region. This process should finely tune the redox environment and thus change an early inflammatory process into a late tissue repair process. We propose Vanin-1 as a key molecule to regulate the GSH-dependent response to oxidative injury in tissue at the epithelial level. Therefore, Vanin/pantetheinase inhibitors could be useful for treatment of damage due to irradiation and pro-oxidant inducers.

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Section: Discussionsupporting

confidence: 69%

Vanin-1^−/− Mice Exhibit a Glutathione-Mediated Tissue Resistance to Oxidative Stress

Berruyer-Pouyet

Martin

Castellano

et al. 2004

Molecular and Cellular Biology

162

161

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“…As noted above, peripheral blood and tissue macrophages produce a number of chemokines and cytokines that are crucial to normal biological function: for example, several cytokines produced by TM are proposed to play key roles in thymocyte maturation and/or selection (25,26). To evaluate the potential impact of HIV-1 infection on TM function we utilized RT-PCR methodology to examine the production of cytokines IL-6, IL-8, TNF-α and M-CSF in TM cultures incubated with or without HIV-1 89.6.…”

Section: Resultsmentioning

confidence: 99%

HIV-1 infection inhibits cytokine production in human thymic macrophages

Rozmysłowicz

Murphy

Conover

et al. 2010

Experimental Hematology

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OBJECTIVE The thymus serves as a critical site of T lymphocyte ontogeny and selection. Thymic infection by HIV-1 is known to disrupt thymocyte maturation by both direct and indirect means, however; the mechanism behind these effects remains poorly defined. Macrophages represent one of the most important peripheral targets of HIV-1 infection, are resident in the thymic stroma, and play a central role in thymocyte maturation. MATERIALS AND METHODS Studies presented here define three primary features and outcomes of thymic macrophages (TM) and HIV-1 infection: (1) The distinctive TM phenotype (surface markers and cytokine production measured by immunofluorescence, FACS and RT-PCR) relative to macrophages from other sources (blood -MDM and bone marrow - BM); (2) Infection of TM by different HIV-1 subtypes (X4, R5 and X4/R5) measured by ELISA and PCR; and (3) The consequences of HIV-1 infection on cytokine production by TM measured by RT-PCR. RESULTS The results demonstrate that TM display a distinctive phenotype of HIV-1 receptors (CD4lo, CXCR4lo, CCR5med, CCR3hi), chemokine production (MIP-1α+, RANTES+, MIP-1b−, SDF-1−), and cytokine production (TNF-a+, IL-8+, M-CSF+, IL-6−) relative to either MDM or BM. TM were infected in vitro with R5 and X4/R5-tropic HIV-1 subtypes, and developed syncytia formation during long-term X4/R5 culture. In contrast, TM supported only transient replication of X4-tropic HIV-1. Lastly, infection of TM with HIV-1 abolished the production of all cytokines tested in long-term in vitro cultures. CONCLUSION Taken together these results indicate that thymic macrophages are a potential direct target of in situ HIV-1 infection, and that this infection may result in the disruption of macrophage functions that govern normal thymocyte maturation.

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“…PTX treatment during daily fractionated irradiation resulted in a significant reduction of the incidence of oral mucositis in the mouse tongue model [11] This may be attributed to a modulation of inflammatory processes which are suggested to be a major component of (early) normal tissue radiation effects [23, 24], including mucositis [25, 26]. Early inflammation is regularly observed during the clinical manifestation of oral epithelial ulceration in patients.…”

Section: Discussionmentioning

confidence: 99%

Early inflammatory changes in radiation-induced oral mucositis

Gruber¹,

Bozsaky²,

Roitinger³

et al. 2017

Strahlenther Onkol

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PurposeEarly inflammation is a major factor of mucosal reactions to radiotherapy. Pentoxifylline administration resulted in a significant amelioration of radiation-induced oral mucositis in the mouse tongue model. The underlying mechanisms may be related to the immunomodulatory properties of the drug. The present study hence focuses on the manifestation of early inflammatory changes in mouse tongue during daily fractionated irradiation and their potential modulation by pentoxifylline.Materials and methodsDaily fractionated irradiation with 5 fractions of 3 Gy/week (days 0–4, 7–11) was given to the snouts of mice. Groups of 3 animals per day were euthanized every second day between day 0 and 14. Pentoxifylline (15 mg/kg, s. c.) was administered daily from day 5 to the day before sacrifice. The expression of the inflammatory proteins TNFα, NF-κB, and IL-1β were analysed.ResultsFractionated irradiation increased the expression of all inflammatory markers. Pentoxifylline significantly reduced the expression of TNFα and IL-1β, but not NF-κB.ConclusionEarly inflammation, as indicated by the expression of the inflammatory markers TNFα, NF-κB, and IL-1β, is an essential component of early radiogenic oral mucositis. Pentoxifylline differentially modulated the expression of different inflammatory markers. The mucoprotective effect of pentoxifylline does not appear to be based on modulation of NF-κB-associated inflammation.

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Inflammatory and Anti-inflammatory Cytokines Regulate the Recovery from Sublethal X Irradiation in Rat Thymus

Cited by 23 publications

References 37 publications

Vanin-1^−/− Mice Exhibit a Glutathione-Mediated Tissue Resistance to Oxidative Stress

Vanin-1^−/− Mice Exhibit a Glutathione-Mediated Tissue Resistance to Oxidative Stress

HIV-1 infection inhibits cytokine production in human thymic macrophages

Early inflammatory changes in radiation-induced oral mucositis

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Inflammatory and Anti-inflammatory Cytokines Regulate the Recovery from Sublethal X Irradiation in Rat Thymus

Cited by 23 publications

References 37 publications

Vanin-1−/− Mice Exhibit a Glutathione-Mediated Tissue Resistance to Oxidative Stress

Vanin-1−/− Mice Exhibit a Glutathione-Mediated Tissue Resistance to Oxidative Stress

HIV-1 infection inhibits cytokine production in human thymic macrophages

Early inflammatory changes in radiation-induced oral mucositis

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Vanin-1^−/− Mice Exhibit a Glutathione-Mediated Tissue Resistance to Oxidative Stress

Vanin-1^−/− Mice Exhibit a Glutathione-Mediated Tissue Resistance to Oxidative Stress