IL-33 is cleaved by mast cell proteases for activation

Stem cell therapy is the use of stem cells to treat or prevent a disease or condition. Parkinson’s disease (PD) is identified as loss of dopamine (DA) release in the striatum. The problem of apply stem cell therapy in PD treatment is the source of cell. This has been solved by iPS cells. Here, we focus on the transplanted cells dopamine release in vivo.

Firstly, we generate a method (treatment with SHH and FGF8) that enable stem cells efficiently differentiate into dopamine-like neurons (pNSC–DAn) in culture. And confirmed the neuron markers of tyrosine hydroxylase (TH) and microtubule-associated protein 2 (Map2).

Next, we combine the two in vivo methods, microdialysis-based HPLC and carbon fiber electrode, to identify the substance as DA and its release site as pNSC–DAn in the striatum of PD rats. HPLC analysis demonstrated the release of DA from pNSC–DAn in response to stimulation with 50 mM K+. The result indicates that the rescued dopamine was released directly from the grafted pNSC–Dan.

Besides, pNSC–DAn kept tyrosine hydroxylase expression and reduced PD-like asymmetric rotation in PD model mice. Compared with that before transplantation, there was a gradual and significant recovery in rotation after transplantation.

To summary, this study shows that human ESC-derived pNSC–DA cells can be integrated into the striatum, making it closer for application of human ESCs in the treatment of PD.

Interleukin-33 (IL-33) is an alarming cytokine, which can activate interleukin 1 receptor-like 1 (IL1RL1) receptor ST2, during type-2 innate immune responses and allergic airway inflammation.

The nuclear domain of IL-33 associates with chromatin and histones H2A-H2B, through a short chromatin-binding motif in its N-terminal part (amino acids 40–58).IL-33 is likely to play a critical role in asthma.

Firstly, we wonder the full-lengthIl-33 as an substrate for mast cell proteases, and found the

There are two major cleavage products of?21 kDa and a minor product of?25 kDa.

Next, we compared the biological activity of full-length IL-33 and mature forms generated by mast cell proteases. Mature IL-33 induces type-2 innate immune responses in vivo, demonstrated by elevated concentrations of IL-5 and IL-13.

The nuclear domain plays a critical role in the regulation of IL-33 cytokine activity.

To summary, this study identifies the central cleavage domain of IL-33 (amino acids 66–111) as an important functional domain of the protein and suggests that regulation with IL-33 cleavage and activation by mast cell and other inflammatory proteases could be useful to reduce IL-33–mediated responses in allergic asthma and other inflammatory diseases.

At last, we show that loss of parkin function in primary cultured neurons causes GluK2 protein to accumulate in cell, potentiates KAR currents and increases KAR-dependent excitotoxicity.

By identifying KAR as a direct target of parkin, our results provide a step ahead towards understanding the mechanism through which parkin modulates synaptic functions. And more, patients with the PARK2 mutation might bene?t from neuroprotective therapy targeting KAR.

Numerologist Warda is hooked on OG-L002 fishing, collecting. And lastly her encouragement comes from socializing along with her companions.