Protein Kinase Serine/Threonine Kinase 24 Positively Regulates Interleukin 17-Induced Inflammation by Promoting IKK Complex Activation.

Abstract

Interleukin 17 (IL-17) is a key inflammatory cytokine that plays a critical role in tissue inflammation and autoimmune diseases. However, its signaling remains poorly understood. In this study, we identified serine/threonine kinase 24 (Stk24) as a positive modulator of IL-17-mediated signaling and inflammation. Stk24 deficiency or knockdown markedly inhibited IL-17-induced phosphorylation of NF-κB and impaired IL-17-induced chemokines and cytokines expression. Stk24 overexpression greatly enhanced IL-17-induced NF-κB activation and expression of chemokines and cytokines in a kinase activity-independent manner. The IL-17-induced inflammatory response was significantly reduced in Stk24-deficient mice. In addition, the severity of experimental autoimmune encephalomyelitis was markedly reduced in mice with a deficiency of Stk24 in non-hematopoietic cells. We further demonstrated that Stk24 directly interacts with TAK1 and IKKβ and promotes the formation of TAK1/IKK complexes, leading to enhanced IKKβ/NF-κB activation and downstream cytokines and chemokines induction. Collectively, our findings suggest that Stk24 plays an important role in controlling IL-17-triggered inflammation and autoimmune diseases and provides new insight into the therapeutic targets of IL-17-mediated inflammatory disease.

• Authors: Yu Jiang, Miao Tian, Wenlong Lin, Xinyuan Wang, Xiaojian Wang
• Journal: Frontiers in immunology (Front Immunol) Vol. 9 Pg. 921 ( 2018) ISSN: 1664-3224 [Print] Switzerland
• PMID: 29760709 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Interleukin-17
• NF-kappa B
• Stk24 protein, mouse
• Protein Serine-Threonine Kinases
• I-kappa B Kinase
• MAP Kinase Kinase Kinases
• MAP kinase kinase kinase 7

Topics

• Animals
• Cell Line
• Cytokines (immunology)
• Encephalomyelitis, Autoimmune, Experimental (genetics, immunology)
• Gene Expression Regulation
• Gene Knockdown Techniques
• I-kappa B Kinase (genetics)
• Inflammation (immunology)
• Interleukin-17 (genetics, immunology)
• MAP Kinase Kinase Kinases (metabolism)
• Mice
• Mice, Knockout
• NF-kappa B (metabolism)
• Phosphorylation
• Protein Serine-Threonine Kinases (genetics)
• Signal Transduction