Expression of protease-activated receptor-1 and -2 in orofacial granulomatosis.
OBJECTIVE
Orofacial granulomatosis (OFG) is a rare condition characterized by non-caseating granulomas in the orofacial region. Protease-Activated Receptors (PARs) play a role in inflammatory diseases in diverse human tissues. The aim of the study was to investigate the expression of PAR-1, PAR-2, MMP-2, MMP-9, COX-1, and COX-2 in tissues taken from OFG patients.


METHODS
PAR-1, PAR-2, MMP-2, MMP-9, COX-1, and COX-2 expression was evaluated by immunohistochemistry in biopsies taken from oral Crohn's disease (five cases), Melkersson-Rosenthal syndrome (MRS) (six cases), cheilitis granulomatosa (five cases) and normal oral mucosa (five cases).


RESULTS
PAR-1 was observed in mononuclear inflammatory cells in edematous/lichenoid lesions, whereas a strong PAR-2 immunostaining was detected in epithelioid histiocytes and giant cells in granulomatous lesions, irrespective of the clinical features (Crohn vs MRS). MMPs and COX-2 were expressed in the inflammatory component of edematous/lichenoid lesions and markedly overexpressed in granulomatous lesions. COX-1 was weakly and variably expressed in both edematous/lichenoid and granulomatous lesions.


CONCLUSIONS
Thus, PAR-1 and PAR-2 expressions were related to the intensity and type of inflammatory response but not to the type of clinical lesion. Simultaneous overexpression of PARs, MMPs and COXs suggests synergism among these proinflammatory receptors and enzymes.
Ketabchi
S
S
Department of Human Pathology and Oncology, University of Florence, Florence, Italy. sheyda.ketabchi@unifi.it
Massi
D
D
Ficarra
G
G
Rubino
I
I
Franchi
A
A
Paglierani
M
M
Simoni
A
A
Capodiferro
S
S
Favia
G
G
Maiorano
E
E
Tarantini
F
F
Cirino
G
G
Santucci
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D003424:Crohn Disease / Q000473:pathology; D051545:Cyclooxygenase 1 / Q000032:analysis; D051546:Cyclooxygenase 2 / Q000032:analysis; D004487:Edema / Q000473:pathology; D015622:Epithelioid Cells / Q000473:pathology; D005260:Female; D015726:Giant Cells / Q000473:pathology; D051261:Granulomatosis, Orofacial / Q000473:pathology*; D006644:Histiocytes / Q000473:pathology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000473:pathology; D017512:Lichenoid Eruptions / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D008556:Melkersson-Rosenthal Syndrome / Q000473:pathology; D008875:Middle Aged; D009059:Mouth Diseases / Q000473:pathology; D009061:Mouth Mucosa / Q000473:pathology; D044463:Receptor, PAR-1 / Q000032:analysis*; D044464:Receptor, PAR-2 / Q000032:analysis*; D012189:Retrospective Studies
D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9