RGD Reference Report - IL-33/ST2 correlates with severity of haemorrhagic fever with renal syndrome and regulates the inflammatory response in Hantaan virus-infected endothelial cells. - Rat Genome Database

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IL-33/ST2 correlates with severity of haemorrhagic fever with renal syndrome and regulates the inflammatory response in Hantaan virus-infected endothelial cells.

Authors: Zhang, Yusi  Zhang, Chunmei  Zhuang, Ran  Ma, Ying  Zhang, Yun  Yi, Jing  Yang, Angang  Jin, Boquan 
Citation: Zhang Y, etal., PLoS Negl Trop Dis. 2015 Feb 6;9(2):e0003514. doi: 10.1371/journal.pntd.0003514. eCollection 2015 Feb.
RGD ID: 40400702
Pubmed: (View Article at PubMed) PMID:25658420
DOI: Full-text: DOI:10.1371/journal.pntd.0003514


BACKGROUND: Hantaan virus (HTNV) causes a severe lethal haemorrhagic fever with renal syndrome (HFRS) in humans. Despite a limited understanding of the pathogenesis of HFRS, the importance of the abundant production of pro-inflammatory cytokines has been widely recognized. Interleukin 33 (IL-33) has been demonstrated to play an important role in physiological and pathological immune responses. After binding to its receptor ST2L, IL-33 stimulates the Th2-type immune response and promotes cytokine production. Depending on the disease model, IL-33 either protects against infection or exacerbates inflammatory disease, but it is unknown how the IL-33/ST2 axis regulates the immune response during HTNV infection.
METHODOLOGY/PRINCIPAL FINDINGS: Blood samples were collected from 23 hospitalized patients and 28 healthy controls. The levels of IL-33 and soluble ST2 (sST2) in plasma were quantified by ELISA, and the relationship between IL-33, sST2 and the disease severity was analyzed. The role of IL-33/sST2 axis in the production of pro-inflammatory cytokines was studied on HTNV-infected endothelial cells. The results showed that the plasma IL-33 and sST2 were significantly higher in patients than in healthy controls. Spearman analysis showed that elevated IL-33 and sST2 levels were positively correlated with white blood cell count and viral load, while negatively correlated with platelet count. Furthermore, we found that IL-33 enhanced the production of pro-inflammatory cytokines in HTNV-infected endothelial cells through NF-κB pathway and that this process was inhibited by the recombinant sST2.
CONCLUSION/SIGNIFICANCE: Our results indicate that the IL-33 acts as an initiator of the "cytokine storm" during HTNV infection, while sST2 can inhibit this process. Our findings could provide a promising immunotherapeutic target for the disease control.

Annotation

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Il1rl1  (interleukin 1 receptor-like 1)
Il33  (interleukin 33)

Genes (Mus musculus)
Il1rl1  (interleukin 1 receptor-like 1)
Il33  (interleukin 33)

Genes (Homo sapiens)
IL1RL1  (interleukin 1 receptor like 1)
IL33  (interleukin 33)


Additional Information