Mycobacterium abscessus—Bronchial Epithelial Cells Cross-Talk Through Type I Interferon Signaling

Zhang, Chongxu; Asif, Huda; Holt, Gregory E.; Griswold, Anthony J.; Campos, Michael; Bejarano, P.A.; Fregien, Nevis; Mirsaeidi, Mehdi

doi:10.3389/fimmu.2019.02888

Cited by 18 publications

(31 citation statements)

References 25 publications

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“…This model is applicable to pulmonary sarcoidosis studies due to the similarly of granuloma to human sarcoidosis. We used C57Bl/6 mice to develop the model as presented in detail elsewhere (15).…”

Section: Mia602 Reduces Inflammation In the Lung Of A Sarcoidosis Moumentioning

confidence: 99%

“…Detained methods were discussed elsewhere (15), As summary, mice were sacrificed on day 14, and the left lungs were harvested as presented earlier. Lungs were filled with 10% buffered formalin and fixed in formalin for at least 72 h before immunohistochemistry (IHC) staining.…”

Section: Immunofluorescence Confocal Microscopymentioning

confidence: 99%

“…Negative controls for all antibodies were made by replacing the primary antibody with non-immunogen IgG. Lung inflammation was scored using the three fields with the highest infiltrate intensity at 100X power magnification as previously presented by our team (15). The area of inflammation was measured and averaged for the three examined high-power fields.…”

Section: Immunofluorescence Confocal Microscopymentioning

confidence: 99%

“…We developed the in vitro model by exposing human peripheral blood mononuclear cells (PBMCs) to microparticles generated from mycobacterial cell walls (14). We expose mouse lungs to the same microparticles to study lung granulomatous disease in vivo (15).…”

Section: Introductionmentioning

confidence: 99%

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Activity of the GHRH Antagonist MIA602 and its Underlying Mechanisms of Action in sarcoidosis

Zhang

Tian

Dreifus

et al. 2020

Preprint

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Growth hormone releasing hormone (GHRH) is a potent stimulator of GH secretion from the pituitary gland. Although GHRH is essential for the growth of immune cells, the regulatory effects of its antagonist in granulomatous disease remains unknown. Here, we report expression of GHRH receptor (R) in human tissue with sarcoidosis granuloma and demonstrate the anti-inflammatory effects of MIA602 (a GHRH antagonist) in two in vitro human granuloma models and an in vivo granuloma model. MIA602 decreases levels of IL2, IL12, and IL17A in in vitro granuloma model. We show further that the anti-inflammatory effect of MIA602 appears to be mediated by reduction in CD45++CD68+ cells in granulomatous tissue and upregulation in PD-1 expression in macrophages. In analysis of expression of proteins involved in the mitochondrial stage of apoptosis, we show that MIA602 increases the levels of caspase 3, BCL-xL/BAK dimer, and MCl-1/Bak dimer in granuloma. These findings indicate that MIA602 may not induce apoptosis. The clinical relevance of our findings further suggest that HGRH-R is potentially a target for treatment of granulomatous disease and MIA602 possibly a novel therapeutic agent for sarcoidosis.

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Section: Mia602 Reduces Inflammation In the Lung Of A Sarcoidosis Moumentioning

confidence: 99%

Section: Immunofluorescence Confocal Microscopymentioning

confidence: 99%

Section: Immunofluorescence Confocal Microscopymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Activity of the GHRH Antagonist MIA602 and its Underlying Mechanisms of Action in sarcoidosis

Zhang

Tian

Dreifus

et al. 2020

Preprint

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“…We previously developed a lung-on-membrane model (LOMM) with a dual chamber including normal bronchial epithelial (NHBE) cells and human microvascular endothelial cells ( Figure 3) [25]. We added a microfluidics system to the LOMM to develop a novel lung on chip.…”

Section: Development Of Lung On Chipmentioning

confidence: 99%

Novel Three-Dimensional Organoid Sarcoidosis Granuloma Model

Calcagno

Zhang

Tian

et al. 2020

Preprint

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Sarcoidosis is a multi-system disorder of granulomatous inflammation which most commonly affects the lungs. Its etiology and pathogenesis are not well defined in part due to the lack of reliable modeling. This article presents the development of a novel in vitro three-dimensional lung-on-chip organoid designed to mimic granuloma formation. A lung on chip fluidic macrodevice with three channels for cell culture insertion was developed and added to the previously developed a lung-on-membrane model. Granulomas were cultured from blood samples of patients with sarcoidosis and then inserted in the air-lung-interface (ALI) of the microchip to create a three-dimensional organoid sarcoidosis model (OSGM). The model was tested for cell viability with fibroblasts. We measured the cytokine profiles in medium of OSGM and compared with lung model without granuloma. Concentration of IL-1beta, Il-6, GM-CSF, and IFN-gamma were found significantly higher in OSGM group. The current model represents the first 3D OSGM created by adding a microfluidics system to a dual-chambered lung on membrane model and introducing developed sarcoid-granuloma to its ALI.

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Activity of the growth hormone‐releasing hormone antagonist MIA602 and its underlying mechanisms of action in sarcoidosis‐like granuloma

et al. 2021

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Objectives. Growth hormone-releasing hormone (GHRH) is a potent stimulator of growth hormone (GH) secretion from the pituitary gland. Although GHRH is essential for the growth of immune cells, the regulatory effects of its antagonist in granulomatous disease remain unknown. Methods. Here, we report expression of GHRH receptor (R) in human tissue with sarcoidosis granuloma and demonstrate the anti-inflammatory effects of MIA602 (a GHRH antagonist) in two in vitro human granuloma models and an in vivo granuloma model using different methods including ELISA, immunohistochemistry, RNAseq analysis and flow cytometry. Results. MIA602 decreases the levels of IL-2, IL-2R, IL-7, IL-12, IL-17A and TNF-a in an in vitro granuloma model. Further, we show that the anti-inflammatory effect of MIA602 appears to be mediated by a reduction in CD45 + CD68 + cells in granulomatous tissue and upregulation in PD-1 expression in macrophages. Analysis of the expression of proteins involved in the mitochondrial stage of apoptosis showed that MIA602 increases the levels of caspase-3, BCL-xL/BAK dimer and MCl-1/Bak dimer in the granuloma. These findings indicate that MIA602 may not induce apoptosis. Conclusions. Our findings further suggest that GHRH-R is potentially a clinical target for the treatment of granulomatous disease and that MIA602 may be used as a novel therapeutic agent for sarcoidosis.

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Mycobacterium abscessus—Bronchial Epithelial Cells Cross-Talk Through Type I Interferon Signaling

Cited by 18 publications

References 25 publications

Activity of the GHRH Antagonist MIA602 and its Underlying Mechanisms of Action in sarcoidosis

Activity of the GHRH Antagonist MIA602 and its Underlying Mechanisms of Action in sarcoidosis

Novel Three-Dimensional Organoid Sarcoidosis Granuloma Model

Activity of the growth hormone‐releasing hormone antagonist MIA602 and its underlying mechanisms of action in sarcoidosis‐like granuloma

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