DPP-4 exacerbates LPS-induced endothelial cells inflammation via integrin-α5β1/FAK/AKT signaling

The Role of Dipeptidyl Peptidase Inhibitors in Pulmonary Diseases

“…In LPS-induced human pulmonary microvascular endothelial cells (HPMECs), DPP-4 knockdown resulted in suppressed chemokine release and hyperpermeability in LPS-exposed HPMECs [ 55 ]. LPS-induced neutrophil–endothelial adhesion, polymorphonuclear neutrophil (PMN) chemotaxis and trans-endothelial migration were suppressed through DPP-4 knockdown in a combined culture of HPMECs and human PMNs [ 55 ].…”

“…In LPS-induced human pulmonary microvascular endothelial cells (HPMECs), DPP-4 knockdown resulted in suppressed chemokine release and hyperpermeability in LPS-exposed HPMECs [ 55 ]. LPS-induced neutrophil–endothelial adhesion, polymorphonuclear neutrophil (PMN) chemotaxis and trans-endothelial migration were suppressed through DPP-4 knockdown in a combined culture of HPMECs and human PMNs [ 55 ]. This was evidenced by decreased AKT, inhibitor of nuclear factor kappa-B kinase subunit (IKK)-α and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 involved in toll-like receptor (TLR)4/NF-κB pathway activation [ 55 ].…”

“…LPS-induced neutrophil–endothelial adhesion, polymorphonuclear neutrophil (PMN) chemotaxis and trans-endothelial migration were suppressed through DPP-4 knockdown in a combined culture of HPMECs and human PMNs [ 55 ]. This was evidenced by decreased AKT, inhibitor of nuclear factor kappa-B kinase subunit (IKK)-α and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 involved in toll-like receptor (TLR)4/NF-κB pathway activation [ 55 ]. Immunoprecipitation and liquid chromatography–tandem mass spectrometry showed promising results for exogenous DPP-4 treatment through increased integrin-α5β1 downstream focal adhesion kinase (FAK)/AKT/NF-κB signaling followed by intercellular adhesion molecule (ICAM)-1 upregulation, thus attenuating endothelial inflammation [ 55 ].…”

“…Experimental data points to therapeutic applications in various respiratory conditions, including pulmonary hypertension, idiopathic pulmonary fibrosis, ALI/ARDS, NSCLC, and asthma. In pulmonary hypertension, DPP-4 promoted, at least partly, endothelial dysfunction and EMT [ 53 , 55 , 56 , 61 ]. Increased RVSP, pulmonary arterial wall thickness and ratio of completely muscularized vessels, pulmonary arterial adventitial fibrosis increases, hypertrophy of right ventricle, and hypertrophy of cardiomyocytes were common findings in animal models and cell lines studied [ 51 , 53 ].…”

The Role of Dipeptidyl Peptidase Inhibitors in Pulmonary Diseases

“…In LPS-induced human pulmonary microvascular endothelial cells (HPMECs), DPP-4 knockdown resulted in suppressed chemokine release and hyperpermeability in LPS-exposed HPMECs [ 55 ]. LPS-induced neutrophil–endothelial adhesion, polymorphonuclear neutrophil (PMN) chemotaxis and trans-endothelial migration were suppressed through DPP-4 knockdown in a combined culture of HPMECs and human PMNs [ 55 ].…”

“…In LPS-induced human pulmonary microvascular endothelial cells (HPMECs), DPP-4 knockdown resulted in suppressed chemokine release and hyperpermeability in LPS-exposed HPMECs [ 55 ]. LPS-induced neutrophil–endothelial adhesion, polymorphonuclear neutrophil (PMN) chemotaxis and trans-endothelial migration were suppressed through DPP-4 knockdown in a combined culture of HPMECs and human PMNs [ 55 ]. This was evidenced by decreased AKT, inhibitor of nuclear factor kappa-B kinase subunit (IKK)-α and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 involved in toll-like receptor (TLR)4/NF-κB pathway activation [ 55 ].…”

“…LPS-induced neutrophil–endothelial adhesion, polymorphonuclear neutrophil (PMN) chemotaxis and trans-endothelial migration were suppressed through DPP-4 knockdown in a combined culture of HPMECs and human PMNs [ 55 ]. This was evidenced by decreased AKT, inhibitor of nuclear factor kappa-B kinase subunit (IKK)-α and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 involved in toll-like receptor (TLR)4/NF-κB pathway activation [ 55 ]. Immunoprecipitation and liquid chromatography–tandem mass spectrometry showed promising results for exogenous DPP-4 treatment through increased integrin-α5β1 downstream focal adhesion kinase (FAK)/AKT/NF-κB signaling followed by intercellular adhesion molecule (ICAM)-1 upregulation, thus attenuating endothelial inflammation [ 55 ].…”

“…Experimental data points to therapeutic applications in various respiratory conditions, including pulmonary hypertension, idiopathic pulmonary fibrosis, ALI/ARDS, NSCLC, and asthma. In pulmonary hypertension, DPP-4 promoted, at least partly, endothelial dysfunction and EMT [ 53 , 55 , 56 , 61 ]. Increased RVSP, pulmonary arterial wall thickness and ratio of completely muscularized vessels, pulmonary arterial adventitial fibrosis increases, hypertrophy of right ventricle, and hypertrophy of cardiomyocytes were common findings in animal models and cell lines studied [ 51 , 53 ].…”

Vildagliptin and Omarigliptin Differentially Bind to DPP‐4 Homodimers and Modulate Osteoclast‐Mediated Bone Resorption

“…The direct actions of both drugs on osteoclasts were supported by the presence of DPP-4 transcripts in mouse multinucleated osteoclasts (Figure 9). Generally, DPP-4 and its substrates are expressed by various cell types, such as enterocytes and endothelial cells (Darmoul et al 1992;Liu et al 2024) (for a review, please see Glorie et al 2016). The functional roles of DPP-4 and its outcomes are likely tissue-specific.…”

The Role of Dipeptidyl Peptidase Inhibitors in Pulmonary Diseases

“…In LPS-induced human pulmonary microvascular endothelial cells (HPMECs), DPP-4 knockdown resulted in suppressed chemokine release and hyperpermeability in LPS-exposed HPMECs [ 55 ]. LPS-induced neutrophil–endothelial adhesion, polymorphonuclear neutrophil (PMN) chemotaxis and trans-endothelial migration were suppressed through DPP-4 knockdown in a combined culture of HPMECs and human PMNs [ 55 ].…”

“…In LPS-induced human pulmonary microvascular endothelial cells (HPMECs), DPP-4 knockdown resulted in suppressed chemokine release and hyperpermeability in LPS-exposed HPMECs [ 55 ]. LPS-induced neutrophil–endothelial adhesion, polymorphonuclear neutrophil (PMN) chemotaxis and trans-endothelial migration were suppressed through DPP-4 knockdown in a combined culture of HPMECs and human PMNs [ 55 ]. This was evidenced by decreased AKT, inhibitor of nuclear factor kappa-B kinase subunit (IKK)-α and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 involved in toll-like receptor (TLR)4/NF-κB pathway activation [ 55 ].…”

“…LPS-induced neutrophil–endothelial adhesion, polymorphonuclear neutrophil (PMN) chemotaxis and trans-endothelial migration were suppressed through DPP-4 knockdown in a combined culture of HPMECs and human PMNs [ 55 ]. This was evidenced by decreased AKT, inhibitor of nuclear factor kappa-B kinase subunit (IKK)-α and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 involved in toll-like receptor (TLR)4/NF-κB pathway activation [ 55 ]. Immunoprecipitation and liquid chromatography–tandem mass spectrometry showed promising results for exogenous DPP-4 treatment through increased integrin-α5β1 downstream focal adhesion kinase (FAK)/AKT/NF-κB signaling followed by intercellular adhesion molecule (ICAM)-1 upregulation, thus attenuating endothelial inflammation [ 55 ].…”

“…Experimental data points to therapeutic applications in various respiratory conditions, including pulmonary hypertension, idiopathic pulmonary fibrosis, ALI/ARDS, NSCLC, and asthma. In pulmonary hypertension, DPP-4 promoted, at least partly, endothelial dysfunction and EMT [ 53 , 55 , 56 , 61 ]. Increased RVSP, pulmonary arterial wall thickness and ratio of completely muscularized vessels, pulmonary arterial adventitial fibrosis increases, hypertrophy of right ventricle, and hypertrophy of cardiomyocytes were common findings in animal models and cell lines studied [ 51 , 53 ].…”

Vildagliptin and Omarigliptin Differentially Bind to DPP‐4 Homodimers and Modulate Osteoclast‐Mediated Bone Resorption

“…The direct actions of both drugs on osteoclasts were supported by the presence of DPP-4 transcripts in mouse multinucleated osteoclasts (Figure 9). Generally, DPP-4 and its substrates are expressed by various cell types, such as enterocytes and endothelial cells (Darmoul et al 1992;Liu et al 2024) (for a review, please see Glorie et al 2016). The functional roles of DPP-4 and its outcomes are likely tissue-specific.…”

The Role of Dipeptidyl Peptidase Inhibitors in Pulmonary Diseases

“…In LPS-induced human pulmonary microvascular endothelial cells (HPMECs), DPP-4 knockdown resulted in suppressed chemokine release and hyperpermeability in LPS-exposed HPMECs [ 55 ]. LPS-induced neutrophil–endothelial adhesion, polymorphonuclear neutrophil (PMN) chemotaxis and trans-endothelial migration were suppressed through DPP-4 knockdown in a combined culture of HPMECs and human PMNs [ 55 ].…”

“…In LPS-induced human pulmonary microvascular endothelial cells (HPMECs), DPP-4 knockdown resulted in suppressed chemokine release and hyperpermeability in LPS-exposed HPMECs [ 55 ]. LPS-induced neutrophil–endothelial adhesion, polymorphonuclear neutrophil (PMN) chemotaxis and trans-endothelial migration were suppressed through DPP-4 knockdown in a combined culture of HPMECs and human PMNs [ 55 ]. This was evidenced by decreased AKT, inhibitor of nuclear factor kappa-B kinase subunit (IKK)-α and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 involved in toll-like receptor (TLR)4/NF-κB pathway activation [ 55 ].…”

“…LPS-induced neutrophil–endothelial adhesion, polymorphonuclear neutrophil (PMN) chemotaxis and trans-endothelial migration were suppressed through DPP-4 knockdown in a combined culture of HPMECs and human PMNs [ 55 ]. This was evidenced by decreased AKT, inhibitor of nuclear factor kappa-B kinase subunit (IKK)-α and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 involved in toll-like receptor (TLR)4/NF-κB pathway activation [ 55 ]. Immunoprecipitation and liquid chromatography–tandem mass spectrometry showed promising results for exogenous DPP-4 treatment through increased integrin-α5β1 downstream focal adhesion kinase (FAK)/AKT/NF-κB signaling followed by intercellular adhesion molecule (ICAM)-1 upregulation, thus attenuating endothelial inflammation [ 55 ].…”

“…Experimental data points to therapeutic applications in various respiratory conditions, including pulmonary hypertension, idiopathic pulmonary fibrosis, ALI/ARDS, NSCLC, and asthma. In pulmonary hypertension, DPP-4 promoted, at least partly, endothelial dysfunction and EMT [ 53 , 55 , 56 , 61 ]. Increased RVSP, pulmonary arterial wall thickness and ratio of completely muscularized vessels, pulmonary arterial adventitial fibrosis increases, hypertrophy of right ventricle, and hypertrophy of cardiomyocytes were common findings in animal models and cell lines studied [ 51 , 53 ].…”

Vildagliptin and Omarigliptin Differentially Bind to DPP‐4 Homodimers and Modulate Osteoclast‐Mediated Bone Resorption

“…The direct actions of both drugs on osteoclasts were supported by the presence of DPP-4 transcripts in mouse multinucleated osteoclasts (Figure 9). Generally, DPP-4 and its substrates are expressed by various cell types, such as enterocytes and endothelial cells (Darmoul et al 1992;Liu et al 2024) (for a review, please see Glorie et al 2016). The functional roles of DPP-4 and its outcomes are likely tissue-specific.…”