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Infection and Immunity, November 2005, p. 7216-7225, Vol. 73, No. 11
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.11.7216-7225.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Peptidoglycan Recognition Protein 2 (N-Acetylmuramoyl-L-Ala Amidase) Is Induced in Keratinocytes by Bacteria through the p38 Kinase Pathway

Haitao Wang, Dipika Gupta, Xinna Li, and Roman Dziarski*

Indiana University School of Medicine—Northwest, Gary, Indiana 46408

Received 23 June 2005/ Returned for modification 7 August 2005/ Accepted 16 August 2005

Human peptidoglycan recognition protein 2 (PGLYRP2) is an N-acetylmuramoyl-L-alanine amidase that hydrolyzes bacterial peptidoglycan and is constitutively produced in the liver and secreted into the blood. Here we demonstrate that PGLYRP2 was not expressed in healthy human skin and had low expression in the eye. However, upon exposure to gram-positive and gram-negative bacteria or cytokines, PGLYRP2 expression was highly induced in keratinocytes and to a lower level in corneal epithelial cells. Expression of PGLYRP2 was not induced in nonepithelial cells. Exposure of keratinocytes to bacteria induced keratinocyte differentiation and stress response and inhibited activation of signal transduction molecules involved in cell proliferation. Induction of PGLYRP2 expression correlated with expression of differentiation markers (cytokeratins and transglutaminase). Bacteria induced activation of p38 mitogen-activated protein kinase (MAPK) in keratinocytes, which was required for the induction of PGLYRP2 expression, because induction of PGLYRP2 transcription by bacteria was inhibited by SB203580 (a specific inhibitor of p38 MAPK) and by a dominant-negative p38 construct. Induction of PGLYRP2 expression by bacteria (in contrast to expression of human ß-defensin-2) was not mediated by Toll-like receptor 2 or 4. PGLYRP2 may function in the skin and the eyes as an inducible scavenger of proinflammatory peptidoglycan.


* Corresponding author. Mailing address: Indiana University School of Medicine—Northwest, 3400 Broadway, Gary, IN 46408. Phone: (219) 980-6535. Fax: (219) 980-6566. E-mail: rdziar{at}iun.edu.

Editor: J. D. Clements


Infection and Immunity, November 2005, p. 7216-7225, Vol. 73, No. 11
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.11.7216-7225.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




This article has been cited by other articles:

  • Wang, M., Liu, L.-H., Wang, S., Li, X., Lu, X., Gupta, D., Dziarski, R. (2007). Human Peptidoglycan Recognition Proteins Require Zinc to Kill Both Gram-Positive and Gram-Negative Bacteria and Are Synergistic with Antibacterial Peptides. J. Immunol. 178: 3116-3125 [Abstract] [Full Text]  
  • Li, X., Wang, S., Wang, H., Gupta, D. (2006). Differential Expression of Peptidoglycan Recognition Protein 2 in the Skin and Liver Requires Different Transcription Factors. J. Biol. Chem. 281: 20738-20748 [Abstract] [Full Text]