Kynurenine pathway as a modulator of inflammation in COPD and its exacerbations.

Airway cell biology and immunopathology(2022)

Cited 0|Views10
No score
Abstract
Introduction: Chronic obstructive pulmonary disease (COPD) is an airway chronic inflammatory disorder. The kynurenine pathway (KP), the major route for tryptophan catabolism, is induced by inflammatory stimuli. The first enzyme of the pathway is indoleamine 2,3-dioxygenase (IDO1). Its activation further leads to the generation of biologically active metabolites with pro- or anti-inflammatory properties. Aims and objectives: Our objective was to determine whether KP is dysregulated in COPD and its exacerbations and therefore could contribute to the impairment of immune response. Methods: Mice chronically exposed to cigarette smoke (CS), mimicking COPD symptoms, were infected with influenza virus (H1N1). The expression of the different enzymes of KP was analyzed in pulmonary extracts by RT-qPCR. Immunohistology of the lung was performed to detect the production of kynurenic and quinolic acids. A human bronchial epithelial cell line BEAS-2B, was incubated with cigarette smoke extract (CSE) and influenza virus particles. The expression of KP enzymes (IDO1, KMO, KYNU) was analyzed by RT-qPCR and correlated with the inflammatory and anti-viral response. Results: The KP is induced by CS in mice lungs and drastically enhanced by viral infections. Immunohistology demonstrated a production of kynurenic and quinolinic acids in epithelia and infiltrating immune cells. IDO1; KMO and KYNU expression were also observed in infected BEAS-2B and their expression was modulated by CSE exposition. Conclusion: KP activation occurs in lung, upon exposition to cigarette smoke or viral infection and could contribute to inflammation regulation and therefore could become a target for the development of new therapeutics.
More
Translated text
Key words
kynurenine pathway,copd,inflammation
AI Read Science
Must-Reading Tree
Example
Generate MRT to find the research sequence of this paper
Chat Paper
Summary is being generated by the instructions you defined