Journal article
ASC-dependent RIP2 Kinase Regulates Reduced PGE2 Production in Chronic Periodontitis
Journal of dental research, Vol.91(9), pp.877-882
09/2012
DOI: 10.1177/0022034512454541
PMCID: PMC3420395
PMID: 22828789
Abstract
Levels of prostaglandin E\n2\n(PGE\n2\n) and its processing enzyme, prostaglandin-endoperoxide-synthase-2/ cyclooxygenase-2 (PTGS2/COX-2), are elevated in actively progressing periodontal lesions, but suppressed in chronic disease.\nCOX-2\nexpression is regulated through inflammatory signaling that converges on the mitogen-activated protein kinase (MAPK) pathway. Emerging evidence suggests a role for the inflammatory adaptor protein, ASC/Pycard, in MAPK activation. We postulated that ASC may represent a mediator of the MAPK-mediated regulatory network of PGE\n2\nproduction. Using RNAi-mediated gene slicing, we demonstrated that ASC regulates\nCOX-2\nexpression and PGE\n2\nproduction in THP1 monocytic cells following infection with\nPorphyromonas gingivalis (Pg)\n. Production of PGE\n2\ndid not require the inflammasome adaptor function of ASC, but was dependent on MAPK activation. Furthermore, the MAP kinase kinase kinase CARD domain-containing protein RIPK2 was induced by\nPg\nin an ASC-dependent manner. Reduced ASC and RIPK2 levels were revealed by orthogonal comparison of the expression of the RIPK family in ASC-deficient THP1 cells with that in chronic periodontitis patients. We show that pharmacological inhibition of RIPK2 represses PGE\n2\nsecretion, and RNAi-mediated silencing of\nRIPK2\nleads to diminished MAPK activation and PGE\n2\nsecretion. These findings identify a novel ASC-RIPK2 axis in the generation of PGE\n2\nthat is repressed in patients diagnosed with chronic adult periodontitis.
Details
- Title: Subtitle
- ASC-dependent RIP2 Kinase Regulates Reduced PGE2 Production in Chronic Periodontitis
- Creators
- D.J Taxman - Department of Microbiology and Immunology, School of Medicine; University of North Carolina, Chapel Hill, NC, USAS Zhang - North Carolina Oral Health Institute, School of Dentistry; University of North Carolina, Chapel Hill, NC, USAY Lei - University of North Carolina at Chapel HillE Holley-Guthrie - Department of Microbiology and Immunology, School of Medicine; University of North Carolina, Chapel Hill, NC, USAS Offenbacher - North Carolina Oral Health Institute, School of Dentistry; University of North Carolina, Chapel Hill, NC, USAJ.P.-Y Ting - Department of Microbiology and Immunology, School of Medicine; University of North Carolina, Chapel Hill, NC, USA
- Resource Type
- Journal article
- Publication Details
- Journal of dental research, Vol.91(9), pp.877-882
- Publisher
- SAGE Publications; Sage CA: Los Angeles, CA
- DOI
- 10.1177/0022034512454541
- PMID
- 22828789
- PMCID
- PMC3420395
- ISSN
- 0022-0345
- eISSN
- 1544-0591
- Language
- English
- Date published
- 09/2012
- Academic Unit
- Periodontics
- Record Identifier
- 9984065801702771
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