Induction of the Expression of the Interleukin-1β Gene in Mouse Spleen by Ionizing Radiation

Ishiguro, Hiroshi; Tsuneoka, Kazuko; Dimchev, Alexander Borrisov; Shikita, Mikio

doi:10.2307/3578216

Cited by 87 publications

(36 citation statements)

References 21 publications

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“…There have been many reports on the effects of ionizing radiation on gene expression of cytokines [21][22][23]. In most experiments, irradiation doses were above 2 Gy and high doses were required to detect radiation-induced cytokine expression.…”

Section: Discussionmentioning

confidence: 99%

Induction of interleukin‐1β and interleukin‐6 mRNA by low doses of ionizing radiation in macrophages

Hosoi

Miyachi

Matsumoto

et al. 2001

Intl Journal of Cancer

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SUMMARYWe have previously reported the antimetastatic effects and augmentation of immune responses, which would be a mechanism of the antimetastatic effects, of 0.1 to 0.2 Gy total body irradiation. To elucidate the cellular mechanisms of the augmentation of immune response, we investigated the effects of low-dose irradiation on gene expression of interleukin-1␤ (IL-1␤) and IL-6 using mouse peritoneal macrophages in vitro. Absolute mRNA quantification was carried out using competitive polymerase chain reaction. Gene expression of IL-1␤ and IL-6 was increased 1 to 2 hr after 2.0 Gy irradiation and then decreased to below the basal expression level 4 hr after irradiation. Irradiation with 0.1 Gy increased IL-6 expression 2 hr after irradiation, but it did not affect IL-1␤ expression. Downregulation of IL-1␤ and IL-6 observed 4 hr after 2.0 Gy irradiation was not observed with 0.1 Gy irradiation. The protein kinase C (PKC) inhibitor H7 and the phosphatidylinositol 3-kinase (PI3-kinase) inhibitor wortmannin inhibited induction of IL-1␤ and IL-6 expression, which suggests that radiation-induced IL-1␤ and IL-6 expression is achieved by PKC-and PI3-kinase-mediated signaling.

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Section: Discussionmentioning

confidence: 99%

Induction of interleukin‐1β and interleukin‐6 mRNA by low doses of ionizing radiation in macrophages

Hosoi

Miyachi

Matsumoto

et al. 2001

Intl Journal of Cancer

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“…Radiation induces the expression of cytokines, such as TNF and IL-1 [22][23][24] . These cytokines stimulate endothelial cells and lymphocytes, resulting in leukocyte adhesion, extravasation and macrophage activation 25) .…”

Section: Discussionmentioning

confidence: 99%

Expression of ICAM-1 and Acute Inflammatory Cell Infiltration in the Early Phase of Radiation Colitis in Rats

Ikeda¹,

Ito²,

Matsuu³

et al. 2000

JRR

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Radiation colitis/ICAM-1/Leukocyte/Myeloperoxidase/RatInflammatory cell infiltration of the colon is observed at an early stage of radiation-induced colitis. The emigration of inflammatory cells from the circulation requires interactions between cell adhesion molecules on the vascular endothelium and molecules on the surface of leukocytes. To elucidate this process, the present work analyzes the kinetics of the expression of intercellular adhesion molecule-1 (ICAM-1) and the accumulation of inflammatory myeloperoxidase (MPO)-positive cells in relation to the appearance of acute radiation colitis prior to an overt radiation-induced ulcer. Colon tissues were obtained from Wistar Kyoto rats at various times after 22.5 Gy irradiation to the rectum. Histologically, crypt depletion and numerous inflammatory cells were observed 4 days after irradiation, and mucosal ulcer 6 days after irradiation. ICAM-1 immunopositivity was present in the endothelial cells of small vessels in the mucosa of both control and irradiated rats. ICAM-1 mRNA expression was detected in normal colon and irradiated colon by reverse transcription-PCR. In Northern blotting, ICAM-1 mRNA levels were found to increase markedly in the irradiated colon compared to the normal colon. In Western blotting, ICAM-1 protein expression also increased with a peak one day after irradiation, and remained elevated up to 6 days thereafter. The number of MPO-positive cells in lamina propria mucosa increased in a time-dependent fashion from 6 h to 6 days after irradiation. These data suggest that up-regulation of ICAM-1 in endothelial cells and accumulation of MPO positive cells play important roles in the development of radiation-induced colonic ulcer.

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“…For example, chemokines CXCL9, CXCL10, and CXCL16, which promote recruitment of effector CD8 and T-helper 1 CD4 T cells, were induced by radiation in different tumors (30)(31)(32). Proinflammatory cytokines induced by radiation include interleukin 1β, tumor necrosis factor α and type 1 and 2 interferons (30,(33)(34)(35)(36). In addition, tumor cells that receive sublethal doses of radiation undergo phenotypic changes that enhance their susceptibility to immune effectors (37)(38)(39).…”

Section: Radiation Response Of Tumors: the Role Of The Immune Systemmentioning

confidence: 99%

Combining Radiotherapy and Cancer Immunotherapy: A Paradigm Shift

Formenti

Demaria²

2013

JNCI: Journal of the National Cancer Institute

890

703

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The therapeutic application of ionizing radiation has been largely based on its cytocidal power combined with the ability to selectively target tumors. Radiotherapy effects on survival of cancer patients are generally interpreted as the consequence of improved local control of the tumor, directly decreasing systemic spread. Experimental data from multiple cancer models have provided sufficient evidence to propose a paradigm shift, whereby some of the effects of ionizing radiation are recognized as contributing to systemic antitumor immunity. Recent examples of objective responses achieved by adding radiotherapy to immunotherapy in metastatic cancer patients support this view. Therefore, the traditional palliative role of radiotherapy in metastatic disease is evolving into that of a powerful adjuvant for immunotherapy. This combination strategy adds to the current anticancer arsenal and offers opportunities to harness the immune system to extend survival, even among metastatic and heavily pretreated cancer patients. We briefly summarize key evidence supporting the role of radiotherapy as an immune adjuvant. A critical appraisal of the current status of knowledge must include potential immunosuppressive effects of radiation that can hamper its capacity to convert the irradiated tumor into an in situ, individualized vaccine. Moreover, we discuss some of the current challenges to translate this knowledge to the clinic as more trials testing radiation with different immunotherapies are proposed.

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Induction of the Expression of the Interleukin-1β Gene in Mouse Spleen by Ionizing Radiation

Cited by 87 publications

References 21 publications

Induction of interleukin‐1β and interleukin‐6 mRNA by low doses of ionizing radiation in macrophages

Induction of interleukin‐1β and interleukin‐6 mRNA by low doses of ionizing radiation in macrophages

Expression of ICAM-1 and Acute Inflammatory Cell Infiltration in the Early Phase of Radiation Colitis in Rats

Combining Radiotherapy and Cancer Immunotherapy: A Paradigm Shift

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