Inspiratory resistive breathing induces MMP-9 and MMP-12 expression in the lung

Abstract

Inspiratory resistive breathing (IRB) is characterized by large negative intrathoracic pressures and was shown to induce pulmonary inflammation in previously healthy rats. Matrix metalloproteinases (MMP)-9 and -12 are induced by inflammation and mechanical stress in the lung. We hypothesized that IRB induces MMP-9 and -12 in the lung. Anesthetized, tracheostomized rats breathed spontaneously through a two-way valve, connected to an inspiratory resistance, with the tidal inspiratory tracheal pressure set at 50% of the maximum. Quietly breathing animals served as controls. After 3 and 6 h of IRB, respiratory mechanics were measured, bronchoalveolar lavage (BAL) was performed, lung injury score was estimated, and lung MMP-9 was estimated by zymography and ELISA. MMP-9 and MMP-12 immunohistochemistry was performed. Isolated normal alveolar macrophages were incubated with BAL from rats that underwent IRB. After 18 h, MMP-9 and -12 levels were measured in supernatants, and immunocytochemistry was performed. Macrophages were treated with IL-1β, IL-6, or TNF-α, and MMP-9 in supernatants was measured. After 6 h of IRB, leukocytes in BAL increased, and IL-1β and IL-6 levels were elevated. Elasticity and injury score were increased after 3 and 6 h of IRB. Lung MMP-9 levels increased after 6 h of IRB. MMP-9 and MMP-12 were detected in alveolar macrophages and epithelial (bronchial/alveolar) cells after 3 and 6 h of IRB. MMP-9 and MMP-12 were found in supernatants after treatment with 6 h of IRB BAL. Cytosolic immunostaining was detected after treatment with 3 and 6 h of IRB BAL. All cytokines induced MMP-9 in culture supernatants. In conclusion, IRB induces MMP-9 and -12 in the lung of previously healthy rats.

Cell-type deconvolution with immune pathways identifies gene networks of host defense and immunopathology in leprosy

“…In Mycobacterium marinum infection of zebrafish, studied as a model for human tuberculosis, MMP-9 has been shown to be required for granuloma formation (40). MMP-9 and MMP-12 cooperate in tissue remodeling in the lung (41) and may coregulate, as MMP-12 upregulated MMP-9 expression in the presence of IL-1β (42). In the gene networks in T-lep lesions, MMP9 and MMP12 were connected by the common gene ontology terms: "chemotaxis" and "tissue remodeling".…”

Can resistive breathing injure the lung? Implications for COPD exacerbations

“…Our aim was to decipher the effects of mechanical stressor (increased inspiratory airway resistance) from the effects of the underlying airway inflammation which is observed in COPD. A series of studies have been performed by adding an inspiratory resistance, so that the tidal pressure during inspiration is set at 50% of maximum ( P i / P i,max =0.5) 9 , 10 . The major findings of these studies are that in a healthy rat lung, inspiratory resistive breathing increases the permeability of the alveolar-capillary membrane of the lung, deranges the respiratory system mechanics, shifting the pressure–volume curve to the right and downward (ie, making the lung less distensible), induces lung inflammation, activates matrix metalloproteinases, and results in acute lung injury and respiratory failure ( Figure 1 ).…”

The solid-state fermentation of Artemisia capillaris leaves with Ganoderma lucidum enhances the anti-inflammatory effects in a model of atopic dermatitis

“…However, another study demonstrated that MMP-9 was upregulated in a mouse model of DNFB-induced atopic dermatitis, and the IL-31 and T-bet gene were also expressed in the ear epidermis (34). MMP-2 and -12 have been shown to be upregulated in the lung by inspiratory resistive breathing (35). Another study demonstrated that the mRNA levels of MMP-1, MMP-7, MMP-10, MMP-14 and MMP-19 were increased independently of COX-2 in monocytes stimulated with LPS (36).…”