biostudies-literatureCao TBTMinistry of EducationKorea Health Technology R&amp;D ProjectKorea Health Technology R&D Project451-472https://www.ebi.ac.uk/biostudies/studies/S-EPMC10359643biostudies-literatureUnknown15(4)<h4>Purpose</h4>Severe asthma (SA) is characterized by persistent airway inflammation and remodeling, followed by lung function decline. The present study aimed to evaluate the role of tissue inhibitor of metalloproteinase-1 (TIMP-1) in the pathogenesis of SA.<h4>Methods</h4>We enrolled 250 adult asthmatics (54 with SA and 196 with non-SA) and 140 healthy controls (HCs). Serum TIMP-1 levels were determined by enzyme-linked immunosorbent assay. The release of TIMP-1 from airway epithelial cells (AECs) in response to stimuli as well as the effects of TIMP-1 on the activations of eosinophils and macrophages were evaluated <i>in vitro</i> and <i>in vivo</i>.<h4>Results</h4>Significantly higher levels of serum TIMP-1 were noted in asthmatics than in HCs, in the SA group than in non-SA group, and in the type 2 SA group than in non-type 2 SA group (<i>P</i> < 0.01 for all). A negative correlation between serum TIMP-1 and FEV₁% values (<i>r</i> = -0.400, <i>P</i> = 0.003) was noted in the SA group. <i>In vitro</i> study demonstrated that TIMP-1 was released from AECs in response to poly I:C, IL-13, eosinophil extracellular traps (EETs) and in coculture with eosinophils. TIMP-1-stimulated mice showed eosinophilic airway inflammation, which was not completely suppressed by steroid treatment. <i>In vitro</i> and <i>in vivo</i> functional studies showed that TIMP-1 directly activated eosinophils and macrophages, and induced the release of EETs and macrophages to polarize toward M2 subset, which was suppressed by anti-TIMP-1 antibody.<h4>Conclusions</h4>These findings suggest that TIMP-1 enhances eosinophilic airway inflammation and that serum TIMP-1 may be a potential biomarker and/or therapeutic target for type 2 SA.Allergy, asthma & immunology researchTissue Inhibitor of Metalloproteinase-1 Enhances Eosinophilic Airway Inflammation in Severe Asthma.PMC10359643HR16C00012019R1A6C1010003Park HSCao TBTRyu MSMoon JYShin YSYang EMQuoc QLChoi YfalseTissue Inhibitor of Metalloproteinase-1 Enhances Eosinophilic Airway Inflammation in Severe Asthma.<h4>Purpose</h4>Severe asthma (SA) is characterized by persistent airway inflammation and remodeling, followed by lung function decline. The present study aimed to evaluate the role of tissue inhibitor of metalloproteinase-1 (TIMP-1) in the pathogenesis of SA.<h4>Methods</h4>We enrolled 250 adult asthmatics (54 with SA and 196 with non-SA) and 140 healthy controls (HCs). Serum TIMP-1 levels were determined by enzyme-linked immunosorbent assay. The release of TIMP-1 from airway epithelial cells (AECs) in response to stimuli as well as the effects of TIMP-1 on the activations of eosinophils and macrophages were evaluated <i>in vitro</i> and <i>in vivo</i>.<h4>Results</h4>Significantly higher levels of serum TIMP-1 were noted in asthmatics than in HCs, in the SA group than in non-SA group, and in the type 2 SA group than in non-type 2 SA group (<i>P</i> < 0.01 for all). A negative correlation between serum TIMP-1 and FEV₁% values (<i>r</i> = -0.400, <i>P</i> = 0.003) was noted in the SA group. <i>In vitro</i> study demonstrated that TIMP-1 was released from AECs in response to poly I:C, IL-13, eosinophil extracellular traps (EETs) and in coculture with eosinophils. TIMP-1-stimulated mice showed eosinophilic airway inflammation, which was not completely suppressed by steroid treatment. <i>In vitro</i> and <i>in vivo</i> functional studies showed that TIMP-1 directly activated eosinophils and macrophages, and induced the release of EETs and macrophages to polarize toward M2 subset, which was suppressed by anti-TIMP-1 antibody.<h4>Conclusions</h4>These findings suggest that TIMP-1 enhances eosinophilic airway inflammation and that serum TIMP-1 may be a potential biomarker and/or therapeutic target for type 2 SA.2023-01-01T00:00:00Z2023 Jul2026-05-04T03:19:00.068Z2025-04-05T14:51:37.418ZS-EPMC103596433707579910.4168/aair.2023.15.4.451