title: Role of TGF-β1 and TNF-α in IL-1β mediated activation of proMMP-9 in pulmonary artery smooth muscle cells: involvement of an aprotinin sensitive protease.
abstract: We investigated the role of TGF-β1 and TNF-α in mediating the effect of IL-1β in activating proMMP-9 and proMMP-2, and the involvement of an aprotinin sensitive protease in this scenario in bovine pulmonary artery smooth muscle cells. IL-1β induces TGF-β1 mediated stimulation of 92kDa proMMP-9 and 72kDa proMMP-2 mRNA and protein expression; whereas, the elevated level of TNF-α promotes activation of proMMP-9 and proMMP-2. Interestingly, TNF-α induced activation of proMMP-9 appeared to be mediated via a 43kDa aprotinin sensitive protease. TNF-α inhibited aprotinin and TIMP-1 mRNA and protein expression, which apparently facilitated the proteolytic conversion of proMMP-9 to MMP-9 with the involvement of the aprotinin sensitive protease. The aprotinin sensitive protease did not activate proMMP-2 under IL-1β stimulation, albeit a marked inhibition of TIMP-2 mRNA and protein expression were elicited by TNF-α. Thus, IL-1β induced stimulation of the two progelatinases occurs via different mechanisms.
authors: Department of Biochemistry and Biophysics, University of Kalyani, West Bengal, India.
authors: Soumitra
authors: S
authors: Roy
authors: Krishna
authors: K
authors: Samanta
authors: Tapati
authors: T
authors: Chakraborti
authors: Animesh
authors: A
authors: Chowdhury
authors: Sajal
authors: S
authors: Chakraborti
mesh_terms: D000818:Animals; D007611:Aprotinin / Q000494:pharmacology*; D002417:Cattle; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004790:Enzyme Induction / Q000187:drug effects / Q000502:physiology; D004792:Enzyme Precursors / Q000096:biosynthesis*; D018093:Gelatinases / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000378:metabolism* / Q000494:pharmacology; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000201:enzymology*; D011651:Pulmonary Artery / Q000166:cytology / Q000201:enzymology*; D012333:RNA, Messenger / Q000096:biosynthesis; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D004792:Enzyme Precursors; D053583:Interleukin-1beta; D012333:RNA, Messenger; D015842:Serine Proteinase Inhibitors; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D007611:Aprotinin; D018093:Gelatinases; C120487:pro-matrix metalloproteinase 9; C069860:progelatinase; D020780:Matrix Metalloproteinase 9