The salt-inducible kinases (SIKs) control a novel molecular switch regulating macrophage polarization. Inhibition of SIKs is reported to promote a macrophage phenotype switch to a 'regulatory'-like phenotype [2-3], that favours resolution of inflammation. This action of SIKs provides a novel intervention point for pharmacological agents with potential as therapeutics for chronic inflammatory diseases.

1. Clark K, MacKenzie KF, Petkevicius K, Kristariyanto Y, Zhang J, Choi HG, Peggie M, Plater L, Pedrioli PG, McIver E et al.. (2012) Phosphorylation of CRTC3 by the salt-inducible kinases controls the interconversion of classically activated and regulatory macrophages. Proc Natl Acad Sci USA, 109 (42): 16986-91. [PMID:23033494]

2. Darling NJ, Toth R, Arthur JS, Clark K. (2017) Inhibition of SIK2 and SIK3 during differentiation enhances the anti-inflammatory phenotype of macrophages. Biochem J, 474 (4): 521-537. [PMID:27920213]

3. Lombardi MS, Gilliéron C, Dietrich D, Gabay C. (2016) SIK inhibition in human myeloid cells modulates TLR and IL-1R signaling and induces an anti-inflammatory phenotype. J Leukoc Biol, 99 (5): 711-21. [PMID:26590148]