Interleukin-1 receptor antagonist attenuates cyclophosphamide-induced mucositis in a murine model

Xiang, Di; Guo, Yiping; Zhang, Jing; Gao, Jin; Lu, Huili; Zhu, Shunying; Wu, Mingyuan; Yu, Yan; Wang, Han

doi:10.1007/s00280-010-1439-1

Cited by 21 publications

(14 citation statements)

References 37 publications

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“…Newer studies have continued to investigate the potential for use of anti-inflammatory agents for mucositis management in preclinical models, although focused on broader outcome measures to link effectiveness with mechanisms. Since the last pathogenesis update, there have been two preclinical studies testing IL-1ra, the naturally occurring IL-1 antagonist [47][48][49]. Both studies found protection against chemotherapy-induced intestinal mucositis and crypt destruction in the small intestine which was attributed to apoptosis prevention.…”

Section: Sophisticated Targeting Of Inflammationmentioning

confidence: 99%

The pathogenesis of mucositis: updated perspectives and emerging targets

Bowen

Al‐Dasooqi²,

Bossi

et al. 2019

Support Care Cancer

121

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Mucositis research and treatment are a rapidly evolving field providing constant new avenues of research and potential therapies. The MASCC/ISOO Mucositis Study Group regularly assesses available literature relating to pathogenesis, mechanisms, and novel therapeutic approaches and distils this to summary perspectives and recommendations. Reviewers assessed 164 articles published between January 2011 and June 2016 to identify progress made since the last review and highlight new targets for further investigation. Findings were organized into sections including established and emerging mediators of toxicity, potential insights from technological advances in mucositis research, and perspective. Research momentum is accelerating for mucositis pathogenesis, and with this has come utilization of new models and interventions that target specific mechanisms of injury. Technological advances have the potential to revolutionize the field of mucositis research, although focused effort is needed to move rationally targeted interventions to the clinical setting.

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Section: Sophisticated Targeting Of Inflammationmentioning

confidence: 99%

The pathogenesis of mucositis: updated perspectives and emerging targets

Bowen

Al‐Dasooqi²,

Bossi

et al. 2019

Support Care Cancer

121

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“…, 5‐FU) and ‐independent ( e.g. , cyclophosphamide) chemotherapy drugs (4, 9, 28). Our results also corroborate recent findings that the induction of HS/PC quiescence before chemotherapy promotes hematopoietic recovery and improves animal survival in lethal‐dose chemotherapy (29–31).…”

Section: Discussionmentioning

confidence: 99%

IL‐1Ra protects hematopoietic cells from chemotoxicity through p53‐induced quiescence

Hao

Qian

Zhu³

et al. 2019

The FASEB Journal

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The protection of constantly proliferating gut epithelia and hematopoietic tissues from cytotoxicity could improve conventional chemotherapy efficacy and widen its therapeutic window. Previously, we reported that, in mouse models, pretreatment of recombinant human IL‐1 receptor antagonist (rhIL‐1Ra) protected both types of vulnerable tissues from chemotherapeutics. Here, we showed that rhIL‐1Ra treatment up‐regulated the protein levels of phosphorylated p38, p53, and p21 and induced transient hematopoietic stem/progenitor cell (HS/PC) quiescence. Knockout of IL‐1 receptor I (IL‐1RI), p53, or p21 alleles and pharmacological inactivation of p38 mapped the rhIL‐1Ra pathway in the induction of HS/PC quiescence. Therefore, rhIL‐1Ra administration before but not after chemotherapy alleviated 5‐fluorouracil‐induced neutropenia. In addition, in vivo and in vitro cell proliferation assays revealed that the rhIL‐1Ra treatment did not affect cancer cell proliferation or chemosensitivity. Lastly, we propose an IL‐1/IL‐1Ra pathway (IL‐1RI → p38 → p53 → p21), which regulates HS/PC quiescence. The rhIL‐1Ra may provide a new route for p53‐based cyclotherapy, which spares normal cells but kills cancer cells during chemotherapy.—Ye, H., Qian, L., Zhu, S., Deng, S., Wang, X., Zhu, J., Chan, G. L., Yu, Y., Han, W. IL‐1Ra protects hematopoietic cells from chemotoxicity through p53‐induced quiescence. FASEB J. 33, 12135‐12145 (2019). http://www.fasebj.org

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“…One good example that can be easily produced and purified in E. coli is recombinant human interleukin-1 receptor antagonist (rhIL-1Ra) 7 . rhIL-1Ra can be produced by E. coli at large scale in soluble form.…”

Section: The Purpose Of Target Protein Determines Its Formmentioning

confidence: 99%

“…A good example of how to express and purify soluble rhIL-1Ra is indicated below. 18 The interleukin-1 receptor antagonist (IL-1Ra) is a protein encoded by the IL1RN gene. IL1Ra was initially called the IL-1 inhibitor and was discovered in 1984.…”

Section: The Purification Of Soluble Recombinant Proteinmentioning

confidence: 99%

The Denaturing and Renaturing are Critical Steps in the Purification of Recombinant Protein in Prokaryotic System

Xiang¹,

Yu²,

Wang³

2012

Protein Purification

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Interleukin-1 receptor antagonist attenuates cyclophosphamide-induced mucositis in a murine model

Abstract: The pretreatment with rhIL-1Ra effectively protected murine gastrointestinal system from clinically relevant cyclophosphamide regimens. The identification of these protective effects of rhIL-1Ra highlights clinical values of this protein for the prevention of CIM.

Cited by 21 publications

References 37 publications

The pathogenesis of mucositis: updated perspectives and emerging targets

The pathogenesis of mucositis: updated perspectives and emerging targets

IL‐1Ra protects hematopoietic cells from chemotoxicity through p53‐induced quiescence

The Denaturing and Renaturing are Critical Steps in the Purification of Recombinant Protein in Prokaryotic System

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