Journal ArticleDOI
Extracellular and nuclear roles of IL-37 after spinal cord injury
Jesús Amo-Aparicio,Alba Sánchez-Fernández,Suzhao Li,Elan Z. Eisenmesser,Cecilia Garlanda,Charles A. Dinarello,Rubèn López-Vales +6 more
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TLDR
It is demonstrated for the first time that translocation to the nucleus is not required for the beneficial actions of this cytokine after SCI and highlights the importance of the extracellular signaling of IL-37 to mediate neuroprotective actions.Abstract:
Interleukin 37 (IL-37) is an anti-inflammatory cytokine of the interleukin 1 family. Transgenic mice expressing the human form of the IL37 gene (hIL-37Tg) display protective effects in several animal models of disease. Previous data from our group revealed that IL-37 limits inflammation after spinal cord injury (SCI) and ameliorates tissue damage and functional deficits. IL-37 can exert its anti-inflammatory effects by translocating to the nucleus or acting as an extracellular cytokine. However, whether this protection after SCI is mediated by translocating to the nucleus, activating of extracellular receptors, or both, is currently unknown. In the present study, we used different transgenic animals to answer this question. We demonstrated that the beneficial effects of IL-37 on functional and histological outcomes after SCI were lost in the lack of the extracellular receptor IL-1R8, indicating that IL-37 induces protection as an extracellular cytokine. On the other hand, transgenic mice with the nuclear function of IL-37 abolished (hIL-37D20ATg) showed significant improvement in locomotor skills and myelin sparing after SCI, indicating that nuclear pathway is not required for the protective actions of IL-37. Moreover, we also showed that the therapeutic effects of the recombinant IL-37 protein are produced only in the presence of the extracellular receptor IL-1R8, further highlighting the importance of the extracellular function of this cytokine after SCI. Finally, we revealed that the administration of recombinant IL-37 protein exerted therapeutic actions when administered in the lesion site but not systemically. This work demonstrated for the first time that translocation of IL-37 to the nucleus is not required for the beneficial actions of this cytokine after SCI and highlights the importance of the extracellular signaling of IL-37 to mediate neuroprotective actions.read more
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Journal ArticleDOI
Current Understanding of IL-37 in Human Health and Disease
Zhangci Su,Xiaoan Tao +1 more
TL;DR: A review of the role of IL-37 in human health and disease, and discusses the potential of IL37 as a therapeutic target and biomarker in inflammatory diseases, autoimmune diseases, and cancer is presented in this paper.
Journal ArticleDOI
Negative Regulation of the IL-1 System by IL-1R2 and IL-1R8: Relevance in Pathophysiology and Disease
TL;DR: The properties of two key regulatory receptors of theIL-1 system are reviewed, IL-1R2, the first decoy receptor identified, and IL- 1R8, a pleiotropic regulator of different IL-2 family members and co-receptor for IL-37, the anti-inflammatory member of the Il-1 family.
Journal ArticleDOI
ACC-BLA functional connectivity disruption in allergic inflammation is associated with anxiety
Leila Gholami-Mahtaj,Morteza Mooziri,Kolsoum Dehdar,Maryam Abdolsamadi,Morteza Salimi,Mohammad Reza Raoufy +5 more
TL;DR: In this paper , the authors evaluated lung and brain inflammatory responses, anxiety-like behavior, in association with oscillatory features of the anterior cingulate cortex (ACC) and basolateral amygdala (BLA), two major brain structures modulating anxiety.
Journal ArticleDOI
Nerve growth factor (NGF) with hypoxia response elements loaded by adeno-associated virus (AAV) combined with neural stem cells improve the spinal cord injury recovery
Qiuji Wu,Ziyue Xiang,Yibo Ying,Zhiyang Huang,Yurong Tu,Chen Min,Jiahui Ye,Haicheng Dou,Sheng Sunren,Xiaoyang Li,Weiyang Ying,Sipin Zhu +11 more
TL;DR: In this article, the authors used adeno-associated virus (AAV) to carry the target gene to transfect neural stem cells to promote the tissue repair and function recovery after spinal cord injury.
Journal ArticleDOI
Association between Serum IL-37 and Spinal Cord Injury: A Prospective Observational Study.
TL;DR: It is proved for the first time that serum IL-37 has prognostic value in patients with SCI and may be used as a prognostic biomarker for SCI.
References
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An RNA-Sequencing Transcriptome and Splicing Database of Glia, Neurons, and Vascular Cells of the Cerebral Cortex
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The Interleukin-1 Family: Back to the Future
TL;DR: The key properties of IL-1 family members are reviewed, with emphasis on pathways of negative regulation and orchestration of innate and adaptive immunity.
Journal ArticleDOI
Basso Mouse Scale for locomotion detects differences in recovery after spinal cord injury in five common mouse strains.
D. Michele Basso,Lesley C. Fisher,Aileen J. Anderson,Lyn B. Jakeman,Dana M. McTigue,Phillip G. Popovich +5 more
TL;DR: The differing behavioral response to SCI suggests inherent genetic factors significantly impact locomotor recovery and must be considered in studies with inbred or genetically engineered mouse strains.
Journal ArticleDOI
Overview of the IL-1 family in innate inflammation and acquired immunity.
TL;DR: Although the inflammatory properties of the IL‐1 family dominate in innate immunity, IL‐2 family member can play a role in acquired immunity and this overview is a condensed update.
Journal ArticleDOI
Interleukin-18 and IL-18 binding protein.
TL;DR: The biology of IL-18 is reviewed as well as its role in human disease, which has been implicated in several autoimmune diseases, myocardial function, emphysema, metabolic syndromes, psoriasis, inflammatory bowel disease, hemophagocytic syndrome, macrophage activation syndrome, sepsis, and acute kidney injury.
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