Modulation of expression of innate immunity markers CXCL5/ENA-78 and CCL20/MIP3alpha by protease-activated receptors (PARs) in human gingival epithelial cells.
Protease-activated receptors (PARs) are G-protein-coupled receptors with an active role in host defense. The two most highly expressed members of the PAR family in gingival epithelial cells (GECs) are PAR1 and PAR2. The major virulence factors of periodontal pathogen Porphyromonas gingivalis are its proteases which can activate PAR2. However, little is known about the function of PARs in GECs when they are activated by their endogenous agonist enzymes. The purpose of this study was to characterize how the expression of innate immune markers is modulated when PAR1 and PAR2 are activated by their agonist enzymes, thrombin and trypsin, respectively. Here, we report that activation of PAR1 and PAR2 induces cell proliferation at low concentration. Activation of PAR via proteolytic activity of thrombin and trypsin induces expression of CXCL5/ENA-78 and CCL20/MIP3alpha in a concentration-dependent manner. Induction of CXCL5 via PAR1 was inhibited in the presence of PAR1 cleavage blocking antibodies and by PAR1 siRNA. The induction of CXCL5 and CCL20 via PAR2 was inhibited by PAR2 siRNA. These findings indicate an active role in innate immune responses by PAR1 and PAR2 in GECs. Modulation of innate immunity by PARs may contribute to co-ordinated and balanced immunosurveillance in GECs.
Rohani
Maryam G
MG
Department of Oral Biology, University of Washington, Seattle, Washington 98195-7132, USA.
Beyer
Richard P
RP
Hacker
Beth M
BM
Dommisch
Henrik
H
Dale
Beverly A
BA
Chung
Whasun O
WO
D019138:Antibodies, Blocking / Q000378:metabolism; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D054418:Chemokine CCL20 / Q000096:biosynthesis* / Q000235:genetics; D054365:Chemokine CXCL5 / Q000096:biosynthesis* / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005881:Gingiva / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate; D034741:RNA, Small Interfering / Q000235:genetics; D044463:Receptor, PAR-1 / Q000235:genetics / Q000378:metabolism*; D044464:Receptor, PAR-2 / Q000235:genetics / Q000378:metabolism*; D013917:Thrombin / Q000494:pharmacology; D014357:Trypsin / Q000494:pharmacology
D019138:Antibodies, Blocking; D054418:Chemokine CCL20; D054365:Chemokine CXCL5; D034741:RNA, Small Interfering; D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; D014357:Trypsin; D013917:Thrombin