Bradykinin stimulates MMP-2 production in guinea pig tracheal smooth muscle cells.
The implication of bradykinin (BK) receptors in the release of the matrix metalloproteinase-2 (MMP-2; gelatinase A) was studied in guinea pig tracheal smooth muscle cells (GP-TSMC). Bradykinin (10(-8)-10(-4) M) induced a time- and concentration-dependent upregulation of MMP-2 production from cultured GP-TSMC. Pretreatment of the GP-TSMC with the bradykinin B2 receptor (BKB2-R) antagonist Hpp-HOE-140 (Hpp-D-Arg0-Hyp3-Thi5-D-Tic7-Oic8-BK; 10(-8)-10(-4) M) significantly inhibited the BK-stimulated upregulation of MMP-2 in GP-TSMC in a concentration-related manner. Conversely, GP-TSMC pretreated with the selective bradykinin B1 receptor (BKB1-R) antagonist R-954 (Ac-Om[Oic2, alpha-MePhe5, D-betaNal7, Ile8]desArg9BK; 10(-8)-10(-4) M) did not show any change in the response to BK. Moreover, the selective BKB2-R agonist Lys0BK (kallidin; 10(-8)-10(-4) M) stimulated whereas the selective BKB1-R agonist desArg9BK (DBK; 10(-8)-10(-4) M) had no effect on MMP-2 release from GP-TSMC. Further, the nonselective cyclooxygenase (COX) enzyme inhibitor indomethacin (IND; 10(-5) M), the glucocorticosteroid dexamethasone (DEX; 1 ng/mL) and the protein synthesis inhibitors, cycloheximide (CHX; 10(-6) M) and actinomycin D (ACT-D; 10(-8) M) also inhibited BK-induced MMP-2 release from GP-TSMC. These results provide the first evidence for the involvement of BK in the release of MMP-2 from airway smooth muscle cells through activation of the BKB2-R. Such response is mostly mediated by the induction of COX and the subsequent production of endogenous prostaglandins (PGs). It could therefore be suggested that MMP-2 might play a role in the process of airway remodeling.
Zaczynska
Ewa
E
Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
Gabra
Bichoy H
BH
Sirois
Pierre
P
D000818:Animals; D001920:Bradykinin / Q000502:physiology*; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006168:Guinea Pigs; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D011453:Prostaglandins / Q000096:biosynthesis; D043782:Receptor, Bradykinin B2 / Q000502:physiology*; D012038:Regeneration; D014132:Trachea / Q000166:cytology* / Q000502:physiology
D011453:Prostaglandins; D043782:Receptor, Bradykinin B2; D011451:Prostaglandin-Endoperoxide Synthases; D020778:Matrix Metalloproteinase 2; D001920:Bradykinin