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Granulocyte-macrophage colony-stimulating factor suppresses induction of type I interferon in infants with severe pneumonia

Background: The underlying mechanisms for infantile bronchopneumonia development remain unknown.

Methods: Peripheral blood mononuclear cell (PBMCs) and serum derived from severe and mild infantile bronchopneumonia were obtained, and the expression of various molecules was detected with enzyme-linked immunosorbent assay and quantitative PCR. Such molecules were also detected in granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced bone marrow-derived NFκB2-/- dendritic cells (DCs) or NIK SMI1 (NF-κB-inducing kinase inhibitor) administrated DCs.

Results: The relative mRNA expression levels of type I interferons (IFNs) (IFN-α4, IFN-β), Th17 cell-associated markers (interleukin-17A, retinoic-acid-receptor-related orphan nuclear receptor gamma, and GM-CSF), and non-canonical NF-κB member (NFκB2) were significantly up-regulated in PBMCs and DCs derived from infantile bronchopneumonia compared with healthy controls. However, compared with Th17 cell-associated markers and non-canonical NF-κB molecules, the expression of IFN-α4 and IFN-β was significantly inhibited in severe infantile bronchopneumonia compared with mild infantile bronchopneumonia. The relative protein expression of the above molecules also showed a similar expression pattern in the PBMCs or serum. NF-κB2 knockout or NIK SMI1 administration could reverse the diminished expression of IFN-β in GM-CSF-induced bone marrow-derived DCs.

Conclusions: GM-CSF-dependent non-canonical NF-κB pathway-mediated inhibition of type I IFNs production in DCs contributes to the development of severe bronchopneumonia in infant.

Impact: Granulocyte-macrophage colony-stimulating factor-dependent non-canonical NF-κB pathway-mediated inhibition of type I IFNs production in dendritic cells is critical for the development of infantile bronchopneumonia. Our findings reveal a possible mechanism underlying the development of severe infantile bronchopneumonia. The results could provide therapeutic molecular target for the treatment of such disease.

 

Comments:

The study you provided examines the underlying mechanisms involved in the development of infantile bronchopneumonia. The researchers focused on the expression of various molecules in peripheral blood mononuclear cells (PBMCs) and dendritic cells (DCs) derived from infants with severe and mild bronchopneumonia, compared to healthy controls.

The results of the study showed that the expression levels of certain molecules were significantly up-regulated in PBMCs and DCs from infants with bronchopneumonia compared to healthy controls. Specifically, the mRNA expression levels of type I interferons (IFN-α4, IFN-β), markers associated with Th17 cells (interleukin-17A, retinoic-acid-receptor-related orphan nuclear receptor gamma, and granulocyte-macrophage colony-stimulating factor [GM-CSF]), and a non-canonical NF-κB member (NFκB2) were increased.

However, the expression of IFN-α4 and IFN-β was significantly inhibited in severe bronchopneumonia compared to mild bronchopneumonia. This finding suggests that the inhibition of type I interferon production may contribute to the development of severe bronchopneumonia in infants.

Furthermore, the researchers found that the GM-CSF-dependent non-canonical NF-κB pathway played a role in inhibiting the production of type I interferons in DCs. When the NFκB2 gene was knocked out or when NIK SMI1 (an NF-κB-inducing kinase inhibitor) was administered, the diminished expression of IFN-β in GM-CSF-induced bone marrow-derived DCs was reversed.

The study concludes that the GM-CSF-dependent non-canonical NF-κB pathway-mediated inhibition of type I interferon production in DCs is critical for the development of infantile bronchopneumonia. These findings provide insights into the possible mechanisms underlying the development of severe bronchopneumonia in infants and suggest potential therapeutic molecular targets for its treatment.

Related Products

Cat.No. Product Name Information
S8941 NIK SMI1 NIK SMI1 is a highly potent and selective NF-κB-inducing kinase (NIK) inhibitor with Ki of 0.23 nM for NIK-catalyzed hydrolysis of ATP to ADP.

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