Salt-inducible kinase (SIK) inhibition is protective in a mouse model of asthma
biorxiv(2021)
Abstract
Interleukin-13 (IL-13) and other Th2 cytokines are important regulators of airway hyper-responsiveness, immune cell infiltration and inflammation in allergic asthma, and are produced when immune cells, such as type 2 innate lymphoid cells (ILC2s) and mast cells, are stimulated with IL-33. Here, we report that the IL-33-dependent secretion of IL-13 from ILC2s is prevented by inhibition of the salt-inducible kinases (SIKs), as we have shown previously in mast cells (Darling NJ et al. , 2021, J. Biol. Chem. doi: 10.1016/j.jbc.2021.100428). We also report that a new SIK inhibitor with improved pharmacokinetic properties suppresses the recruitment of eosinophils to the lungs and serum immunoglobulin E (IgE) levels in the Alternaria alternata-induced model of allergic asthma. Our results suggest that drugs targeting SIK isoforms may have therapeutic potential for the treatment of asthma.
### Competing Interest Statement
The authors have declared no competing interest.
* BALF
: bronchoalveolar lavage fluid
BMMC
: bone marrow-derived mast cells
CCL
: (C-C motif) ligand
GM-CSF
: granulocyte-macrophage colony stimulating factor
IgE
: immunoglobulin E
IL
: interleukin
ILC2
: type 2 innate lymphoid cell
PGE2
: prostaglandin E2
SIK
: salt-inducible kinase
TNF
: tumour necrosis factor
WT
: wild type
MoreTranslated text
Key words
asthma,sik,salt-inducible
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