Physiological stress exacerbates murine colitis by enhancing proinflammatory cytokine expression that is dependent on IL-18

Matsunaga, Hisayuki; Hokari, Ryota; Ueda, Toshihide; Kurihara, Chie; Hozumi, Hideaki; Higashiyama, Masaaki; Okada, Yoshikiyo; Watanabe, Chikako; Komoto, Shunsuke; Nakamura, Mitsuyasu; Kawaguchi, Atsushı; Nagao, Shigeaki; Sekiyama, Atsuo; Miura, Soichiro

doi:10.1152/ajpgi.00482.2010

Cited by 28 publications

(20 citation statements)

References 52 publications

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“…Moreover, Matsunaga et al . () also found that IL‐18 was involved in the pathophysiology of the proinflammatory response in colonic inflammation under psychologically stressful conditions, using IL‐18 knockout mice and an anti‐IL‐18 antibody. Furthermore, Verri et al .…”

Section: Discussionmentioning

confidence: 97%

“…Several studies have contributed to the current state of knowledge regarding the role of IL‐18 in tissue injury (Verri et al ., ; Matsunaga et al ., ; Wyburn et al ., ). Wyburn et al .…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have contributed to the current state of knowledge regarding the role of IL-18 in tissue injury (Verri et al, 2007;Matsunaga et al, 2011;Wyburn et al, 2013). Wyburn et al (2013) recently demonstrated that doxorubicin, an anticancer agent that inhibits topoisomerase II, induced nephrotoxicity in an IL-18-dependent manner.…”

Section: Bjpmentioning

confidence: 99%

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Targeted inhibition of IL‐18 attenuates irinotecan‐induced intestinal mucositis in mice

Lima-Júnior

Freitas

Wong

et al. 2014

British J Pharmacology

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Background and Purpose Intestinal mucositis is a common side‐effect of irinotecan‐based cancer chemotherapy regimens. This mucositis is associated with cytokine activation and NO synthesis. Production of IL‐18 is up‐regulated in patients suffering from inflammatory bowel disease. Therefore, we have investigated the role of IL‐18 in the pathogenesis of irinotecan‐induced intestinal mucositis. Experimental Approach Wild type (WT), IL‐18 or caspase‐1 knockout mice were treated with either saline or irinotecan (60 mg·kg−1 per 4 days, i.p.) or the IL‐18 binding protein (IL‐18bp, 10 mg·kg−1) before irinotecan. On day 5, diarrhoea was monitored and proximal intestinal strips were obtained for histopathology, in vitro gut contractility, myeloperoxidase (MPO) and inducible NOS (iNOS) activity, and detection of IL‐18 expression. Key Results Irinotecan induced severe diarrhoea accompanied by intestinal injury (villi shortening and increased crypt depth). Additionally, irinotecan treatment increased MPO and iNOS activity, iNOS immunostaining and IL‐18 expression in WT mice compared with saline treatment. The IL‐18 production was associated with macrophages. In vitro, intestinal smooth muscle strips were hyperresponsive to ACh after irinotecan treatment. Increases in MPO and iNOS activity, intestinal contractility and diarrhoea were prevented in caspase‐1 knockout and IL‐18 knockout mice, and in IL‐18bp‐treated WT mice. Furthermore, the Survival of irinotecan‐treated mice was increased and iNOS immunoexpression and IL‐18 production prevented in IL‐18 knockout mice. Conclusions and Implications Targeting IL‐18 function may be a promising therapeutic approach to decreasing the severity of intestinal mucositis during irinotecan treatment regimens.

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Section: Discussionmentioning

confidence: 97%

“…Several studies have contributed to the current state of knowledge regarding the role of IL‐18 in tissue injury (Verri et al ., ; Matsunaga et al ., ; Wyburn et al ., ). Wyburn et al .…”

Section: Discussionmentioning

confidence: 99%

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Targeted inhibition of IL‐18 attenuates irinotecan‐induced intestinal mucositis in mice

Lima-Júnior

Freitas

Wong

et al. 2014

British J Pharmacology

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“…Multidirectional functional consequences of neuro-immune interactions have been appreciated for decades (Besedovsky et al, 1983; Stead et al, 1987), with emphasis given to stress-mediated alterations in immune responses and, conversely, cytokine-mediated alterations in CNS including animal behavior and brain activity (Matsunaga et al, 2011; Serrats et al, 2010). As an example, efferent vagal nerve signals were shown to attenuate macrophage activity leading to anti-inflammatory responses in the intestine (de Jonge et al, 2005; Rosas-Ballina et al, 2011; Wang et al, 2003).…”

Section: Neuro-immune Interactions In Health and Diseasementioning

confidence: 99%

Neuro-Immune Interactions at Barrier Surfaces

Veiga-Fernandes

Mucida

2016

Cell

222

171

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Multidirectional interactions between the nervous and immune systems have been documented in homeostasis and pathologies ranging from multiple sclerosis to autism, and from leukemia to acute and chronic inflammation. Recent studies have addressed this crosstalk using cell-specific targeting, novel sequencing, imaging and analytical tools, shedding light on unappreciated mechanisms of neuro-immune regulation. This review focuses on neuro-immune interactions at barrier surfaces, mostly the gut, but also including the skin and the airways, areas densely populated by neurons and immune cells that constantly sense and adapt to tissue-specific environmental challenges.

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“…Interleukin-18 (IL-18) is a pro-inflammatory cytokine which has been linked with varying degrees of evidence to diseases as diverse as cardiovascular disease (Jefferis et al, 2011), asthma (Ma et al, 2012), inflammatory bowel disease (Siegmund, 2010; Matsunaga et al, 2011; Rivas et al, 2011), acute kidney injury (Ho, Fard & Maisel, 2010), and type 1 (Smyth et al, 2008) and type 2 diabetes (Thorand et al, 2005; Hivert et al, 2009), either through associations with IL-18 itself or with its receptor or binding protein. The IL-18 receptor belongs to the interleukin-1/Toll-like receptor superfamily, and is encoded by two genes— IL18R1 and IL18RAP —which encode a ligand-binding subunit (commonly known as IL-18R α ) and accessory protein (IL-18R β ) subunit, respectively (Dinarello, 2009).…”

Section: Introductionmentioning

confidence: 99%

Identification of a truncated splice variant of IL-18 receptor alpha in the human and rat, with evidence of wider evolutionary conservation

Booker

Grattan

2014

PeerJ

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Interleukin-18 (IL-18) is a pro-inflammatory cytokine which stimulates activation of the nuclear factor kappa beta (NF-κB) pathway via interaction with the IL-18 receptor. The receptor itself is formed from a dimer of two subunits, with the ligand-binding IL-18Rα subunit being encoded by the IL18R1 gene. A splice variant of murine IL18r1, which has been previously described, is formed by transcription of an unspliced intron (forming a ‘type II’ IL18r1 transcript) and is predicted to encode a receptor with a truncated intracellular domain lacking the capacity to generate downstream signalling. In order to examine the relevance of this finding to human IL-18 function, we assessed the presence of a homologous transcript by reverse transcription-polymerase chain reaction (RT-PCR) in the human and rat as another common laboratory animal. We present evidence for type II IL18R1 transcripts in both species. While the mouse and rat transcripts are predicted to encode a truncated receptor with a novel 5 amino acid C-terminal domain, the human sequence is predicted to encode a truncated protein with a novel 22 amino acid sequence bearing resemblance to the ‘Box 1’ motif of the Toll/interleukin-1 receptor (TIR) domain, in a similar fashion to the inhibitory interleukin-1 receptor 2. Given that transcripts from these three species are all formed by inclusion of homologous unspliced intronic regions, an analysis of homologous introns across a wider array of 33 species with available IL18R1 gene records was performed, which suggests similar transcripts may encode truncated type II IL-18Rα subunits in other species. This splice variant may represent a conserved evolutionary mechanism for regulating IL-18 activity.

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Physiological stress exacerbates murine colitis by enhancing proinflammatory cytokine expression that is dependent on IL-18

Cited by 28 publications

References 52 publications

Targeted inhibition of IL‐18 attenuates irinotecan‐induced intestinal mucositis in mice

Targeted inhibition of IL‐18 attenuates irinotecan‐induced intestinal mucositis in mice

Neuro-Immune Interactions at Barrier Surfaces

Identification of a truncated splice variant of IL-18 receptor alpha in the human and rat, with evidence of wider evolutionary conservation

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