Journal
NATURE CHEMICAL BIOLOGY
Volume 15, Issue 9, Pages 907-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41589-019-0344-0
Keywords
-
Categories
Funding
- Korea Health Technology R&D Project 'Strategic Center of Cell and Bio Therapy' through Korea Health Industry Development Institute - Ministry of Health Welfare, Korea [HI17C2085]
- 'Korea Research-Driven Hospital' through Korea Health Industry Development Institute - Ministry of Health Welfare, Korea [HI14C1277]
- National Research Foundation of Korea - Korea Government [2018R1C1B5086482]
- National Research Foundation of Korea [2018R1C1B5086482] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Ask authors/readers for more resources
Toll-like receptor (TLR)/myeloid differentiation primary response protein (MYD88) signaling aggravates sepsis by impairing neutrophil migration to infection sites. However, the role of intracellular fatty acids in TLR/MYD88 signaling is unclear. Here, inhibition of fatty acid synthase by C75 improved neutrophil chemotaxis and increased the survival of mice with sepsis in cecal ligation puncture and lipopolysaccharide-induced septic shock models. C75 specifically blocked TLR/MYD88 signaling in neutrophils. Treatment with GSK2194069 that targets a different domain of fatty acid synthase, did not block TLR signaling or MYD88 palmitoylation. De novo fatty acid synthesis and CD36-mediated exogenous fatty acid incorporation contributed to MYD88 palmitoylation. The binding of IRAK4 to the MYD88 intermediate domain and downstream signal activation required MYD88 palmitoylation at cysteine 113. MYD88 was palmitoylated by ZDHHC6, and ZDHHC6 knockdown decreased MYD88 palmitoylation and TLR/MYD88 activation upon lipopolysaccharide stimulus. Thus, intracellular saturated fatty acid-dependent palmitoylation of MYD88 by ZDHHC6 is a therapeutic target of sepsis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available