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

Abstract

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-κB 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. 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-κB 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. Innate immunity is an early defense mechanism against pathogens in both vertebrates and invertebrates (1Janeway C. Medzhitov R. Annu. Rev. Immunol. 2002; 20: 197-216Crossref PubMed Scopus (6094) Google Scholar, 2Hoffmann J.A. Kafatos F.C. Janeway C.A. Ezekowitz R.A. Science. 1999; 284: 1313-1318Crossref PubMed Scopus (2143) Google Scholar). The innate immune system includes pattern recognition molecules that recognize pathogens through a series of motifs called pathogen-associated molecular patterns (1Janeway C. Medzhitov R. Annu. Rev. Immunol. 2002; 20: 197-216Crossref PubMed Scopus (6094) Google Scholar, 2Hoffmann J.A. Kafatos F.C. Janeway C.A. Ezekowitz R.A. Science. 1999; 284: 1313-1318Crossref PubMed Scopus (2143) Google Scholar). Peptidoglycan recognition proteins (PGRPs) 4The abbreviations used are: PGLYRP or PGRP, peptidoglycan recognition protein; TLR, Toll-like receptor; NF-κB, nuclear factor κB; CREB, cAMP-response element-binding protein; RACE, rapid amplification of cDNA ends; ERK, extracellular signal-regulated kinase; ChIP, chromatin immunoprecipitation; Abs, antibodies; kbp, kilobase pair. 4The abbreviations used are: PGLYRP or PGRP, peptidoglycan recognition protein; TLR, Toll-like receptor; NF-κB, nuclear factor κB; CREB, cAMP-response element-binding protein; RACE, rapid amplification of cDNA ends; ERK, extracellular signal-regulated kinase; ChIP, chromatin immunoprecipitation; Abs, antibodies; kbp, kilobase pair. belong to a novel family of innate immune molecules that are highly conserved between invertebrates and vertebrates and recognize bacteria through the cell wall component, peptidoglycan. PGRPs were first identified in insects (3Yoshida H. Kinoshita K. Ashida M. J. Biol. Chem. 1996; 271: 13854-13860Abstract Full Text Full Text PDF PubMed Scopus (392) Google Scholar, 4Kang D. Liu G. Lundstrom A. Gelius E. Steiner H. Proc. Natl. Acad. Sci. U. S. A. 1998; 95: 10078-10082Crossref PubMed Scopus (399) Google Scholar) and then in mammals (4Kang D. Liu G. Lundstrom A. Gelius E. Steiner H. Proc. Natl. Acad. Sci. U. S. A. 1998; 95: 10078-10082Crossref PubMed Scopus (399) Google Scholar, 5Liu C. Gelius E. Liu G. Steiner H. Dziarski R. J. Biol. Chem. 2000; 275: 24490-24499Abstract Full Text Full Text PDF PubMed Scopus (161) Google Scholar, 6Dziarski R. Mol. Immunol. 2004; 40: 877-886Crossref PubMed Scopus (295) Google Scholar, 7Liu C. Xu Z. Gupta D. Dziarski R. J. Biol. Chem. 2001; 276: 34686-34694Abstract Full Text Full Text PDF PubMed Scopus (292) Google Scholar). Mammals have a family of 4 PGRPs, which were initially named PGRP-S, PGRP-L, PGRP-Iα, and PGRP-Iβ (for “short,” “long,” or “intermediate” transcripts, respectively), by analogy to insect PGRPs (7Liu C. Xu Z. Gupta D. Dziarski R. J. Biol. Chem. 2001; 276: 34686-34694Abstract Full Text Full Text PDF PubMed Scopus (292) Google Scholar). Recently, the Human Genome Organization Gene Nomenclature Committee changed their names to peptidoglycan recognition protein 1, 2, 3, and 4 (PGLYRP1, PGLYRP2, PGLYRP3, and PGLYRP4), and this new nomenclature is used in this article. Mammalian PGLYRPs were originally thought to be pattern recognition receptors similar to insect PGRPs, however, recent data have demonstrated an effector role for these molecules. PGLYRP1 is produced in granulocytes and is antibacterial (7Liu C. Xu Z. Gupta D. Dziarski R. J. Biol. Chem. 2001; 276: 34686-34694Abstract Full Text Full Text PDF PubMed Scopus (292) Google Scholar, 8Dziarski R. Platt K.A. Gelius E. Steiner H. Gupta D. Blood. 2003; 102: 689-697Crossref PubMed Scopus (151) Google Scholar, 9Tydell C.C. Yount N. Tran D. Yuan J. Selsted M.E. J. Biol. Chem. 2002; 277: 19658-19664Abstract Full Text Full Text PDF PubMed Scopus (112) Google Scholar, 10Tydell C.C. Yuan J. Tran P. Selsted M.E. J. Immunol. 2006; 176: 1154-1162Crossref PubMed Scopus (101) Google Scholar). PGLYRP1-deficient mice show increased sensitivity to bacterial infection and deficiency in killing of phagocytosed bacteria (8Dziarski R. Platt K.A. Gelius E. Steiner H. Gupta D. Blood. 2003; 102: 689-697Crossref PubMed Scopus (151) Google Scholar). PGLYRP2 has an N-acetylmuramoyl-l-alanine amidase activity (11Wang Z.-M. Li X. Cocklin R.R. Wang M. Wang M. Fukase K. Inamura S. Kusumoto S. Gupta D. Dziarski R. J. Biol. Chem. 2003; 278: 49044-49052Abstract Full Text Full Text PDF PubMed Scopus (189) Google Scholar, 12Sang Y. Ramanathan B. Ross C.R. Blecha F. Infect. Immun. 2005; 73: 7133-7141Crossref PubMed Scopus (36) Google Scholar), which hydrolyzes the amide bond between MurNAc and l-Ala and thus removes stem peptides from the peptidoglycan molecule (13Valinger Z. Ladesic B. Tomasic J. Biochim. Biophys. Acta. 1982; 701: 63-71Crossref PubMed Scopus (53) Google Scholar, 14Mollner S. Braun V. Arch. Microbiol. 1984; 140: 171-177Crossref PubMed Scopus (28) Google Scholar, 15Vanderwinkel E. De Vlieghere M. De Pauw P. Cattalini N. Ledoux V. Gigot D. ten Have J.-P. Biochim. Biophys. Acta. 1990; 1039: 331-338Crossref PubMed Scopus (21) Google Scholar). PGLYRP2 produced in the liver is identical to the serum N-acetylmuramoyl amidase (16Zhang Y. van der Fits L. Voerman J.S. Melief M.-J. Laman J.D. Wang M. Wang H. Wang M. Li X. Gupta D. Dziarski R. Biochim. Biophys. Acta. 2005; 1752: 34-46Crossref PubMed Scopus (55) Google Scholar). Digestion of peptidoglycan amidase or of peptidoglycan Melief R. Google Scholar, P. J. Steiner H. J. Biol. Chem. 2003; 278: Full Text Full Text PDF PubMed Scopus Google Scholar). and are against and against and mice against infection X. Wang M. J. Wang H. Li X. Gupta D. Dziarski R. J. Biol. Chem. 2006; Full Text Full Text PDF PubMed Scopus Google Scholar). initially demonstrated differential and expression of the PGLYRPs in human (7Liu C. Xu Z. Gupta D. Dziarski R. J. Biol. Chem. 2001; 276: 34686-34694Abstract Full Text Full Text PDF PubMed Scopus (292) Google Scholar). Recently, we have the expression and of PGLYRP2 mRNA in human and cell H. Gupta D. Li X. Dziarski R. Infect. Immun. 2005; 73: PubMed Scopus Google Scholar). PGLYRP2 has a high constitutive expression in the expression in of the and and is not expressed in healthy human skin. PGLYRP2 mRNA is also not expressed in cultured human keratinocytes but is highly induced upon exposure to and bacteria. PGLYRP2 mRNA is also induced by bacteria in cultured human but is expression or in human and the cell line or H. Gupta D. Li X. Dziarski R. Infect. Immun. 2005; 73: PubMed Scopus Google Scholar). The of PGLYRP2 expression of and and requires of protein H. Gupta D. Li X. Dziarski R. Infect. Immun. 2005; 73: PubMed Scopus Google Scholar). The of this study to the for this differential of PGLYRP2 expression in hepatocytes and keratinocytes and to transcription factors that are in the constitutive expression of pglyrp2 in hepatocytes and in the of pglyrp2 transcription in keratinocytes by bacteria. and from were from and in Human were used between the and and the were in for H. Gupta D. Li X. Dziarski R. Infect. Immun. 2005; 73: PubMed Scopus Google Scholar). The hepatocyte cell line and the human cell line Toll-like 2 Dziarski R. M. Gupta D. Infect. Immun. 2001; PubMed Scopus Google Scholar) were cultured in and were 2 of or were not for data that exposure of to bacteria not the high constitutive expression of PGLYRP2 in these and from human liver and were from and from cultured keratinocytes and the In the keratinocytes were cultured the for and the H. Gupta D. Li X. Dziarski R. Infect. Immun. 2005; 73: PubMed Scopus Google Scholar). the used an the for transcription start site for pglyrp2 by two different and the from from and keratinocytes and from the The used for of to of and used for the of cDNA the in the and for a and The were an and then by used in this used for used for the used for the PGLYRP2 used for used for used for to PGLYRP2 promoter to to in a new The of PGLYRP2 mRNA also by liver cDNA from The were the the a and an The were a by and were for pglyrp2 pglyrp2 to of the start by from and the and of the is to The promoter region and the human in were for and the that used for the the but different The a to of the start were the from Z. Dziarski R. Wang K. Gupta D. J. Immunol. 2001; PubMed Scopus Google Scholar). used for and are in for and were to and were by and of of pglyrp2 and were cultured in in were in the different pglyrp2 or for keratinocytes and for and In keratinocytes were and of a or the constitutive of Dziarski R. M. Gupta D. Infect. Immun. 2001; PubMed Scopus Google Scholar), or Dziarski R. M. Gupta D. Infect. Immun. 2001; PubMed Scopus Google Scholar) and the of or H. Gupta D. Li X. Dziarski R. Infect. Immun. 2005; 73: PubMed Scopus Google Scholar). were and of a or the of M. M. 1998; PubMed Scopus Google Scholar) or c-Jun H. C. J. D. M. Full Text PDF PubMed Scopus Google Scholar). were keratinocytes were in for and then bacteria for and cell were H. Gupta D. Li X. Dziarski R. Infect. Immun. 2005; 73: PubMed Scopus Google Scholar). were bacteria for and cell were Dziarski R. M. Gupta D. Infect. Immun. 2001; PubMed Scopus Google Scholar). were not and were of the pglyrp2 of the pglyrp2 and transcription activity and in the cell Z. Dziarski R. Wang K. Gupta D. J. Immunol. 2001; PubMed Scopus Google Scholar). The are expressed a of or of the or and were cultured in for were and in the were and nuclear were D. S. Dziarski R. J. Biol. Chem. 1996; 271: Full Text Full Text PDF PubMed Scopus Google Scholar). to regions in the pglyrp2 promoter in were and nuclear proteins for D. S. Dziarski R. J. Biol. Chem. 1996; 271: Full Text Full Text PDF PubMed Scopus Google Scholar). the that an nuclear were for by the to and were from and to Sp1, and were from of were an of or for were then and the were by D. S. Dziarski R. J. Biol. Chem. 1996; 271: Full Text Full Text PDF PubMed Scopus Google Scholar). a from the keratinocytes and were cultured in of keratinocytes for and not The in for and then for The were and in and 4 between The were a and were to in were for 4 and in were used for against Sp1, or not The were for 4 to the and the of the pglyrp2 promoter that the NF-κB, Sp1, or were the in that a different region of the promoter were used of and were cultured and for cell were and to D. S. Dziarski R. J. Biol. Chem. 1996; 271: Full Text Full Text PDF PubMed Scopus Google Scholar). of by an to of the of PGLYRP2 mRNA and of the pglyrp2 have that PGLYRP2 mRNA is differentially expressed in human H. Gupta D. Li X. Dziarski R. Infect. Immun. 2005; 73: PubMed Scopus Google Scholar). the and transcription factors that are in this expression of PGLYRP2 we first the of the PGLYRP2 mRNA by two different and from keratinocytes and two that the to or of the start keratinocytes bacteria were the keratinocytes the of PGLYRP2 mRNA in keratinocytes to bacteria. from also which the high constitutive expression of PGLYRP2 in The liver cDNA in different of these identical to the that a in the and this the is the transcription start site of PGLYRP2 mRNA and the region the promoter. of the start site both and in the data The pglyrp2 promoter not have a or a however, transcription were the distal promoter 2 NF-κB, Sp1, and whereas the proximal promoter binding PGLYRP2 mRNA and pglyrp2 in the and and of the pglyrp2 have and in this study that PGLYRP2 mRNA is differentially expressed in the liver and the that this differential expression between the liver and we the expression of PGLYRP2 mRNA in the human liver cell line and in human have high constitutive expression of PGLYRP2 which not in the of bacteria In keratinocytes not PGLYRP2 however, of by or induced high expression H. Gupta D. Li X. Dziarski R. Infect. Immun. 2005; 73: PubMed Scopus Google Scholar). regions of the promoter that the expression of PGLYRP2 in keratinocytes and we pglyrp2 first 2 or regions of the start and these were and and pglyrp2 transcription by and were highly expressed in and the expression not in the of bacteria not that the for high constitutive expression of PGLYRP2 in the liver the region of the promoter and we have this the proximal promoter. promoter activity in however, but not highly induced by both and 2, and that the that are for of pglyrp2 transcription in keratinocytes bacteria the region of the pglyrp2 which we are the distal promoter. is expressed or induced in 2, and which to bacteria by NF-κB and mRNA expression Dziarski R. M. Gupta D. Infect. Immun. 2001; PubMed Scopus Google Scholar). the region of the distal promoter that is for the of PGLYRP2 expression in keratinocytes we the expression of pglyrp2 promoter the region were not expressed in keratinocytes but were induced upon exposure to however, the is and the promoter is to regions the distal promoter were for the of pglyrp2 transcription in keratinocytes bacteria The first region is between and and the is between and the promoter transcription factor binding are located these two regions of the pglyrp2 NF-κB, Sp1, and and constitutive expression of PGLYRP2 in requires the region of the promoter we the expression of pglyrp2 promoter this region of the promoter. The is the expressed in The of by expression of the the The region of the promoter between and is for the expression of pglyrp2 in however, sequences in the region of mRNA the expression of PGLYRP2 mRNA of in constitutive and not in the of bacteria not that different regions of the pglyrp2 promoter are in and of pglyrp2 transcription in In this study we the region between and of the pglyrp2 this region is for the expression of PGLYRP2 mRNA in from NF-κB in the pglyrp2 two regions of pglyrp2 promoter for of PGLYRP2 mRNA binding for different transcription NF-κB and NF-κB is a transcription factor in the of immune responses and we NF-κB is in the of expression of The pglyrp2 promoter has 2 NF-κB and of the start these two binding were used for the binding of proteins by the from keratinocytes not proteins that or nuclear from keratinocytes or proteins that both and of proteins that these is rapid and binding is in both and The of binding of nuclear proteins from keratinocytes to the and sequences and The binding of nuclear proteins to both the and sequences by an of a or a but not by NF-κB binding that the binding of nuclear proteins from keratinocytes bacteria to the and the pglyrp2 promoter is the proteins that the and sequences the PGLYRP2 promoter we the binding in the of against different of the NF-κB and and different against were against and but not or the binding of nuclear proteins to both the and sequences the pglyrp2 promoter that keratinocytes and the of and NF-κB that both and the pglyrp2 promoter. is to the pglyrp2 promoter in in keratinocytes the chromatin of keratinocytes induced of to the pglyrp2 promoter that not in demonstrated by the in the NF-κB by amplification in the of the binding region is also amplification of an region of the promoter used a to amplification of the pglyrp2 promoter both of The the is The of is in the to and of requires of of in keratinocytes by of in the In of the binding of NF-κB to the pglyrp2 promoter in and in and that the NF-κB is of and of pglyrp2 in for the induced transcription of pglyrp2 in keratinocytes bacteria. first for the of the of pglyrp2 the family of which in the of of and the of the of PGLYRP2 mRNA in keratinocytes both and then the for the of in the of and the expression of constitutive of used in the but not the the induced expression of pglyrp2 binding of NF-κB to the the pglyrp2 promoter is for the induced transcription of pglyrp2 in keratinocytes bacteria. or or were for expression in keratinocytes bacteria. or the pglyrp2 promoter the induced expression of pglyrp2 that both and are and are important for the of pglyrp2 in keratinocytes bacteria. In we have of protein and of PGLYRP2 expression by both and a of in keratinocytes bacteria. we the role of protein in the of but not NF-κB in keratinocytes to bacteria data that of in the of NF-κB and transcription of from an the pglyrp2 and this for of region important in the of expression of PGLYRP2 in keratinocytes to bacteria is between and of the start region has binding for transcription the role of in transcription of pglyrp2 in keratinocytes bacteria. this binding site used to binding of nuclear proteins from keratinocytes by the from keratinocytes but not from keratinocytes proteins that to the rapid and the binding and by The binding of nuclear proteins to the by an of but not by binding that the binding of nuclear from keratinocytes bacteria to the site the pglyrp2 promoter is the proteins that the the pglyrp2 promoter we the binding in the of and The against but not the binding of nuclear proteins to the the pglyrp2 promoter that keratinocytes and binding of the protein to the site the pglyrp2 promoter. the chromatin is to the PGLYRP2 promoter in to the promoter in keratinocytes demonstrated by of the in the by the amplification in the of the binding region also amplification of an region of the promoter used a to amplification of the pglyrp2 promoter both of The the is binding of to the site is for the induced expression of pglyrp2 in keratinocytes bacteria. the site or the binding were for expression in keratinocytes bacteria. the binding site of the promoter the induced expression of pglyrp2 by that the site is for the transcription of pglyrp2 in keratinocytes bacteria. and c-Jun to an the pglyrp2 and for of pglyrp2 in region between and of the pglyrp2 promoter is for the expression of PGLYRP2 in the hepatocyte cell and this region binding for different transcription factors two binding motifs and and an of the start and nuclear proteins from or both the these regions of the promoter. of nuclear proteins to the site the and the site not and were these binding proteins from to the the and the binding an of but not by the binding identified the proteins in that to this the pglyrp2 promoter. to different of the and and to and proteins were in to and the in the the is also identified the binding against and c-Jun a in the binding pattern of nuclear proteins to the but to CREB, and not the binding pattern not data that transcription factors and c-Jun in nuclear from to the the the pglyrp2 promoter. the chromatin c-Jun and are to the pglyrp2 promoter in in c-Jun and were to the promoter in demonstrated by the in the the the and the amplification in the of the binding region also amplification of an region of the promoter used a to amplification of the pglyrp2 promoter both of The the this site is for constitutive expression of PGLYRP2 in for we the of expression of the pglyrp2 promoter and to the in The the whereas the is and the binding of the binding site the constitutive expression of PGLYRP2 mRNA by The also expression the however, we were to binding this region of the promoter by or by that the binding site and binding of c-Jun and to the pglyrp2 promoter are for the constitutive transcription of pglyrp2 in the role of and c-Jun in the constitutive expression of pglyrp2 in we the of of these and c-Jun pglyrp2 transcription in that and c-Jun are two transcription factors for constitutive expression of pglyrp2 in In this study we have identified the transcription start site for human PGLYRP2 the pglyrp2 and identified the that are in the differential expression of the pglyrp2 PGLYRP2 is not expressed in human or in cultured however, is induced in keratinocytes upon exposure to bacteria. In PGLYRP2 is expressed in the liver and the hepatocyte cell and the of expression not upon exposure to bacteria. that in keratinocytes is sequences the distal of the whereas constitutive expression in requires the proximal region of the promoter. that of PGLYRP2 mRNA in keratinocytes bacteria has an for the transcription factor The NF-κB family is for the of immune responses and includes the proteins and which to the NF-κB S. Annu. Rev. Immunol. 1998; PubMed Scopus Google Scholar). is to protein and in the and of is for the of S. Annu. Rev. Immunol. 1998; PubMed Scopus Google Scholar, M. Y. Annu. Rev. Immunol. 2000; PubMed Scopus Google Scholar). that both NF-κB binding and the proteins and and both are for the of pglyrp2 transcription in is in the study that two both for activity A. D. 2004; Full Text Full Text PDF PubMed Scopus Google Scholar). have the for the two both by the of of and the NF-κB the for transcription factor NF-κB in the of PGLYRP2 NF-κB is not for or NF-κB upon exposure to bacteria and Dziarski R. M. Gupta D. Infect. Immun. 2001; PubMed Scopus Google Scholar) but not data are in the of human PGRPs in by E. and A. P. 2005; PubMed Scopus Google Scholar). The human pglyrp2 promoter has binding for Sp1, transcription transcription factors a family of proteins that Sp1, and transcription factors sequences and are in the of and expressed of keratinocytes J. Full Text PDF PubMed Scopus Google Scholar, A. F. G. G. R. S. J. 2004; Full Text Full Text PDF PubMed Scopus Google Scholar, J. Biol. Chem. 2002; 277: Full Text Full Text PDF PubMed Scopus Google Scholar). that the is to the protein and is for the of PGLYRP2 mRNA in human keratinocytes bacteria. data also the role of in of in Induction of pglyrp2 transcription in keratinocytes to bacteria is protein H. Gupta D. Li X. Dziarski R. Infect. Immun. 2005; 73: PubMed Scopus Google Scholar). data in this NF-κB a of transcription in an of or the of NF-κB by from also a role for in the of both NF-κB 2005; PubMed Scopus Google Scholar, H. B. C. 2004; PubMed Scopus Google Scholar) and X. J. Biol. Chem. 2004; Full Text Full Text PDF PubMed Scopus Google Scholar, M. C.A. J. Biol. Chem. 2002; 277: Full Text Full Text PDF PubMed Scopus Google Scholar). The in the recognition of bacteria and in the of PGLYRP2 expression in human keratinocytes has not and are the extracellular receptors and bacteria in of and are also in the of human PGRPs in by E. and A. P. 2005; PubMed Scopus Google Scholar). in keratinocytes of PGLYRP2 in to bacteria is not through or these receptors are in the of H. Gupta D. Li X. Dziarski R. Infect. Immun. 2005; 73: PubMed Scopus Google Scholar, K. H. N. A. K. M. J. Sci. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar, M. V. G. C. R. M. C. P. J. D. M. J. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar). that the receptors and in the of PGLYRP2 and peptides in keratinocytes are In to expression of PGLYRP2 mRNA in liver is constitutive and the expression of pglyrp2 in hepatocytes is regulated by sequences between and of the promoter. proximal region of the promoter has sequences for The family of transcription factors of the and proteins that to the and both constitutive and induced expression of M. Liu Z. E. Biol. PubMed Scopus Google Scholar). proteins or In also a of the family of transcription data that proteins c-Jun and the the pglyrp2 promoter and this binding site is for the constitutive expression of PGLYRP2 mRNA in the human liver cell a of the expression of pglyrp2 by which that are that the high expression of pglyrp2 in liver and c-Jun expression of the by and these proteins show of the which is the this site not that be binding the region of the promoter. by proteins be to be in however, be and be data that sequences of that be in the expression of In the we these regions to in the of pglyrp2 transcription in liver The amidase activity of PGLYRP2 in of the amide bond between MurNAc and l-Ala and thus removes stem peptides from the peptidoglycan The in of this activity of peptidoglycan amidase the activity of extracellular peptidoglycan Melief R. Google Scholar, P. J. Steiner H. J. Biol. Chem. 2003; 278: Full Text Full Text PDF PubMed Scopus Google Scholar), which is through R. Dziarski R. H. M. J. Biol. Chem. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar, R. Gupta D. Infect. Immun. 2005; 73: PubMed Scopus Google Scholar) and also the recognition of peptidoglycan which is by and requires M. D. D. J. Biol. Chem. 2003; 278: Full Text Full Text PDF PubMed Scopus Google of peptidoglycan a the that is a from the stem of a peptidoglycan the M. D. D. J. Biol. Chem. 2003; 278: Full Text Full Text PDF PubMed Scopus Google and PGLYRP2 have antibacterial of peptidoglycan amidase have a to activity of have a antibacterial or which The of PGLYRP2 in human keratinocytes by bacteria and high constitutive expression in the liver the role and of the amidase in innate immune responses to bacterial infections. The differential expression the for the of PGLYRP2 amidase to be constitutive or Human is to bacteria and pathogens and have to of bacteria and bacterial peptidoglycan. PGLYRP2 amidase be expressed in keratinocytes in the of high of bacteria or in the of bacteria that are not of the the liver is to bacteria and bacterial which to a systemic and of PGLYRP2 in the serum and systemic of the transcription factors and that are in this differential expression of PGLYRP2 Dziarski for of the and the