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Infection and Immunity, September 2009, p. 4002-4008, Vol. 77, No. 9
0019-9567/09/$08.00+0     doi:10.1128/IAI.00176-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Staphylococcus aureus Induces Microglial Inflammation via a Glycogen Synthase Kinase 3β-Regulated Pathway{triangledown}

Yi-Lin Cheng,1 Chi-Yun Wang,1,2 Wei-Ching Huang,1,2,3 Cheng-Chieh Tsai,1,2,4 Chia-Ling Chen,3 Ching-Fen Shen,1,5 Chia-Yu Chi,1,5,6 and Chiou-Feng Lin1,2,3*

Institute of Clinical Medicine,1 Institute of Basic Medical Sciences,2 Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan,3 Department of Nursing, Chung Hwa University of Medical Technology, Tainan 701, Taiwan,4 Department of Pediatrics, National Cheng Kung University Medical College Hospital, Tainan 701, Taiwan,5 Division of Infectious Diseases, National Health Research Institutes, Tainan 701, Taiwan6

Received 16 February 2009/ Returned for modification 12 May 2009/ Accepted 4 July 2009

A proinflammatory role for glycogen synthase kinase 3β (GSK-3β) has been demonstrated. Here, we addressed its roles on heat-inactivated Staphylococcus aureus-induced microglial inflammation. Heat-inactivated S. aureus induced tumor necrosis factor alpha (TNF-{alpha}) and nitric oxide (NO) production, at least in part, via a Toll-like receptor 2-regulated pathway. Neutralization of TNF-{alpha} largely blocked heat-inactivated S. aureus-induced NO. Heat-inactivated S. aureus activated GSK-3β, and inhibiting GSK-3β reduced TNF-{alpha} production as well as inducible NO synthase (iNOS)/NO biosynthesis. While activation of NF-{kappa}B was essential for heat-inactivated S. aureus-induced TNF-{alpha} and NO, inhibiting GSK-3β blocked heat-inactivated S. aureus-induced NF-{kappa}B p65 nuclear translocation. Additionally, inhibiting GSK-3β enhanced heat-inactivated S. aureus-induced interleukin-10 (IL-10) production (IL-10 is an anti-inflammatory cytokine which inhibits TNF-{alpha} production). Neutralization of IL-10 reduced TNF-{alpha} downregulation caused by GSK-3β inhibition. These results suggest that GSK-3β regulates heat-inactivated S. aureus-induced TNF-{alpha} and NO production in microglia mainly by activating NF-{kappa}B and probably by inhibiting IL-10.

* Corresponding author. Mailing address: Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, 1 University Road, Tainan 701, Taiwan. Phone: 886-6-2353535-4240. Fax: 886-6-3028162. E-mail: cflin{at}mail.ncku.edu.tw

{triangledown} Published ahead of print on 13 July 2009.

Editor: A. J. Bäumler

Infection and Immunity, September 2009, p. 4002-4008, Vol. 77, No. 9
0019-9567/09/$08.00+0     doi:10.1128/IAI.00176-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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