Potential of IL-33 for Preventing the Kidney Injury via Regulating the Lipid Metabolism in Gout Patients

Duan, Lihua; Huang, Yan; Su, Qun; Lin, Qingyan; Wen, Lu; Luo, Jiao; Yu, Bing; He, Yan; Qian, Hongyan; Liu, Yuan; Chen, Jie; Shi, Guixiu

doi:10.1155/2016/1028401

Cited by 23 publications

(15 citation statements)

References 28 publications

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“…It was recently reported that serum IL-33 expression was increased in gout patients compared to healthy controls and positively correlated with the inflammatory indicator C-reactive protein 14 , 15 . IL-33, a member of the IL-1 family, binds to the receptor complex, consisting of IL-33 specific ST2 and IL-1 receptor accessory protein IL-1RAcp, to elicit biological functions in inflammation, autoimmune response and homeostasis 16 , 17 .…”

Section: Introductionmentioning

confidence: 96%

IL-33/ST2 induces neutrophil-dependent reactive oxygen species production and mediates gout pain

Yin

Liu

et al. 2020

Theranostics

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Objective: Gout, induced by monosodium urate (MSU) crystal deposition in joint tissues, provokes severe pain and impacts life quality of patients. However, the mechanisms underlying gout pain are still incompletely understood. Methods: We established a mouse gout model by intra-articularly injection of MSU crystals into the ankle joint of wild type and genetic knockout mice. RNA-Sequencing, in vivo molecular imaging, Ca 2+ imaging, reactive oxygen species (ROS) generation, neutrophil influx and nocifensive behavioral assays, etc. were used. Results: We found interleukin-33 (IL-33) was among the top up-regulated cytokines in the inflamed ankle. Neutralizing or genetic deletion of IL-33 or its receptor ST2 (suppression of tumorigenicity) significantly ameliorated pain hypersensitivities and inflammation. Mechanistically, IL-33 was largely released from infiltrated macrophages in inflamed ankle upon MSU stimulation. IL-33 promoted neutrophil influx and triggered neutrophil-dependent ROS production via ST2 during gout, which in turn, activated transient receptor potential ankyrin 1 (TRPA1) channel in dorsal root ganglion (DRG) neurons and produced nociception. Further, TRPA1 channel activity was significantly enhanced in DRG neurons that innervate the inflamed ankle via ST2 dependent mechanism, which results in exaggerated nociceptive response to endogenous ROS products during gout. Conclusions: We demonstrated a previous unidentified role of IL-33/ST2 in mediating pain hypersensitivity and inflammation in a mouse gout model through promoting neutrophil-dependent ROS production and TRPA1 channel activation. Targeting IL-33/ST2 may represent a novel therapeutic approach to ameliorate gout pain and inflammation.

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Section: Introductionmentioning

confidence: 96%

IL-33/ST2 induces neutrophil-dependent reactive oxygen species production and mediates gout pain

Yin

Liu

et al. 2020

Theranostics

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“…Our previous study has shown that the serum IL-33 level was predominantly increased in gout patients when compared to healthy controls, and the increased IL-33 expression might play a protective role in kidney injury by regulating lipid metabolism in gout (25). In this study, we recruited more participants to compare levels of IL-33 in gout patients and healthy volunteers.…”

Section: Resultsmentioning

confidence: 99%

IL-33 Ameliorates the Development of MSU-Induced Inflammation Through Expanding MDSCs-Like Cells

Shang

Wei

et al. 2019

Front. Endocrinol.

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Interleukin-33 (IL-33), a member of the IL-1 superfamily, has been shown to play a critical role in many diseases through regulating the immune cell responses, including myeloid-derived suppressor cells (MDSCs). Our previous study demonstrated that IL-33 might play a protective role in kidney injury in gout patients by regulating the lipid metabolism. However, the role of IL-33in the development of MSU-induced inflammation remains elusive. In this study, an increased IL-33 expression was observed in gout patients, which was positively correlated with inflammatory marker CRP. To explore the effects and mechanisms of the increased IL-33 expression in the gout patients, the anti-ST2 antibody and exogenous recombinant IL-33 were used in MSU-induced peritonitis animal model that mimics human gout. Compared with control group, mice with exogenous recombinant IL-33 significantly ameliorated the inflammatory cells infiltration, while blockage of IL-33 signaling by anti-ST2 had no effect on the development of MSU-induced peritonitis. Furthermore, the crucial inflammatory cytokine IL-1β was markedly decreased in IL-33-treated mice. Besides that, a large number of anti-inflammatory MDSCs with CD11b + Gr1 int F4/80 + phenotype was observed in the IL-33-treated mice, and adoptive transfer of IL-33-induced MDSCs (CD11b + Gr1 int F4/80 + ) markedly inhibited the IL-1β production in MSU-induced peritonitis. In conclusion, our data provide clear evidences that the increased expression of IL-33 in the gout patients might be due to a cause of self-negative regulation, which inhibits the development of MSU-induced inflammation through expanding MDSCs. Thus, IL-33 might serve as a promising therapeutic target for gout.

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“…The role for sST2 appears to be stronger than the role of IL-33, as demonstrated by the lack of association between the increased IL-33 levels and kidney injury in diabetic nephropathy, with such increase possibly associated with diabetic disease [26]. Taken together with the evidences of other studies, which are not included in the detailed review as they do not directly deal with the conditions investigated in this work [35,36], such retrievals suggest that the serum levels of sST2 are more relevant in investigating the deterioration of kidney function with respect to the serum levels of IL-33.…”

Section: Il-33/st2 Axis Involvement In Diabetic Kidney Disease or mentioning

confidence: 98%

IL33/ST2 Axis in Diabetic Kidney Disease: A Literature Review

2019

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Interleukin-33 (IL-33) is a cytokine belonging to the IL-1 family, playing a role in inflammatory, infectious and autoimmune diseases and expressed in the cellular nucleus in several tissues. High levels of IL-33 are expressed in epithelial barrier tissues and endothelial barriers. ST2 is a receptor for IL-33, expressed selectively on a subset of Th2 cells, mediating some of their functions. The IL-33/ST2 axis plays an important role in several acute and chronic inflammatory diseases, including asthma and rheumatoid arthritis. Different disorders are related to the activity of IL-33, ST2, or their axis, including cardiovascular disease or renal disturbances. Therefore, in the present work, a literature review was conducted, covering the period from 1 January 2000 to 30 November 2018, in PubMed, ScienceDirect, and Google Scholar database, to assess the involvement of the IL-33/ST2 axis in diabetic kidney disease. 6 articles directly dealing with the argument were identified, highlighting a clear link between IL-33/ST2 axis and diabetic kidney disease or related nephropathy. Overall, the involvement of ST2 seems to be more predictive than IL-33, especially in investigating the deterioration of kidney function; however, both compounds are pivotal in the field of renal diseases. Future studies are required to confirm the scientific evidences on larger and more heterogeneous cohorts.

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Potential of IL-33 for Preventing the Kidney Injury via Regulating the Lipid Metabolism in Gout Patients

Cited by 23 publications

References 28 publications

IL-33/ST2 induces neutrophil-dependent reactive oxygen species production and mediates gout pain

IL-33/ST2 induces neutrophil-dependent reactive oxygen species production and mediates gout pain

IL-33 Ameliorates the Development of MSU-Induced Inflammation Through Expanding MDSCs-Like Cells

IL33/ST2 Axis in Diabetic Kidney Disease: A Literature Review

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