Expression of receptor for advanced glycation end products in sarcoid granulomas

Ilaria Campo, Patrizia Morbini, Michele Zorzetto, Carmine Tinelli, Enrico Brunetta, Chiara Villa, Cristina Bombieri, Mariaclara Cuccia, Carlo Agostini, Valeria Bozzi, Angelica Facoetti, Ilaria Ferrarotti, Paola Mazzola, Roberta Scabini, Gianpietro Semenzato, Pier Franco Pignatti, Ernesto Pozzi, Maurizio Luisetti

Research output: Contribution to journalArticle

Abstract

Rationale: The receptor for advanced glycation end products (RAGE) engages a number of ligands implicated in inflammatory processes. The RAGE coding gene maps to the 6p21.32 region, close to the genes DRB1 and BTNL2, which are associated with sarcoidosis. Objectives: We investigated a possible implication of RAGE in sarcoid granulomas. Methods: RAGE and major ligands (N-ε-carboxy-methyl-lysine [CML], S100A12, and S100B) expression was investigated by immunostaining of 99 paraffin-embedded biopsies of sarcoid tissues, and expression patterns were determined. Among the three RAGE gene single-nucleotide polymorphisms investigated, -374 T/A was selected, characterized in terms of transcriptional effect (immunocytochemistry and real-time polymerase chain reaction), and its frequency was determined in DNA extracted from biopsies. Measurements and Results: RAGE, CML, S100A12, and S100B immunoreactivity was observed in all sarcoid granulomas, although at different intensities. The degree of RAGE expression significantly correlated with the degree of S100A12 expression. The -374 TT/AT genotypes, associated with higher RAGE transcriptional activity, were more frequent in the sarcoidosis biopsy group than in control subjects, and the association was confirmed in a second, independent series of 101 patients with sarcoidosis. Conclusions: We showed the association of RAGE and its ligands with sarcoidosis and suggest that an intrinsic genetic factor could be in part involved in its expression. In Italian patients, the -374 T/A polymorphism seems to be significantly associated with this disease.

Original languageEnglish
Pages (from-to)498-506
Number of pages9
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume175
Issue number5
DOIs
Publication statusPublished - Mar 1 2007

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Keywords

  • Genetics
  • Immunohistochemistry
  • Ligands
  • Real-time polymerase chain reaction

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Campo, I., Morbini, P., Zorzetto, M., Tinelli, C., Brunetta, E., Villa, C., Bombieri, C., Cuccia, M., Agostini, C., Bozzi, V., Facoetti, A., Ferrarotti, I., Mazzola, P., Scabini, R., Semenzato, G., Pignatti, P. F., Pozzi, E., & Luisetti, M. (2007). Expression of receptor for advanced glycation end products in sarcoid granulomas. American Journal of Respiratory and Critical Care Medicine, 175(5), 498-506. https://doi.org/10.1164/rccm.200601-136OC