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J. Biol. Chem., Vol. 281, Issue 30, 20738-20748, July 28, 2006

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Differential Expression of Peptidoglycan Recognition Protein 2 in the Skin and Liver Requires Different Transcription Factors^*

From the Indiana University School of Medicine-Northwest, Gary, Indiana 46408

Human peptidoglycan recognition protein 2 (PGLYRP2) is an N-acetylmuramoyl-L-alanine amidase that hydrolyzes bacterial peptidoglycan and is differentially expressed in the two major organs in the human body, liver and skin. PGLYRP2 has a high constitutive expression in the liver but is not expressed in healthy human skin. PGLYRP2 mRNA is also not expressed in cultured human keratinocytes but is highly induced upon exposure to bacteria. In this study we identified the transcription start site for pglyrp2 and demonstrated that the differential expression of PGLYRP2 in hepatocytes and keratinocytes is regulated by different transcription factors whose binding sequences are located in different regions of the pglyrp2 promoter. Induction of pglyrp2 in keratinocytes is regulated by sequences in the distal region of the promoter and requires transcription factors NF-B and Sp1, whereas constitutive expression of pglyrp2 in a hepatocyte cell line is regulated by sequences in the proximal region of the promoter and requires transcription factors c-Jun and ATF2. Regulation of constitutive and inducible expression of pglyrp2 is important for systemic and local innate immune responses to bacterial infections.

Received for publication, February 2, 2006 , and in revised form, May 19, 2006.

^* This work was supported by United States Public Health Service Grants AI28797 and AI56395 from the National Institutes of Health. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Both authors contributed equally to this work.

² Current address: Dept. of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA.

³ To whom correspondence should be addressed. Tel.: 219-980-6557; Fax: 219-980-6566; E-mail: dgupta{at}iun.edu.

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