# Interleukin-13 Treatment of Living Lung Tissue Model Alters the Metabolome and Proteome—A Nano-DESI MS Metabolomics and Shotgun Proteomics Study

## TL;DR

This study uses a new method to analyze how IL-13 affects lung cells, revealing changes in metabolism and proteins that could help understand asthma better.

## Contribution

The study introduces nano-DESI MS for in vivo metabolomic analysis of ALI lung-cell layers and links metabolic changes to proteomic profiles.

## Key findings

- Nano-DESI MS successfully monitored molecular transport and metabolic responses in ALI lung cells.
- IL-13 exposure led to metabolic remodeling correlated with proteomic changes after histamine and corticosteroid treatments.
- The study identified new markers that could guide future research on lung diseases like asthma.

## Abstract

Asthma is a chronic respiratory disease with one of the largest numbers of cases in the world; thus, constant investigation and technical development are needed to unravel the underlying biochemical mechanisms. In this study, we aimed to develop a nano-DESI MS method for the in vivo characterization of the cellular metabolome. Using air–liquid interface (ALI) cell layers, we studied the role of Interleukin-13 (IL-13) on differentiated lung epithelial cells acting as a lung tissue model. We demonstrate the feasibility of nano-DESI MS for the in vivo monitoring of basal–apical molecular transport, and the subsequent endogenous metabolic response, for the first time. Conserving the integrity of the ALI lung-cell layer enabled us to perform temporally resolved metabolomic characterization followed by “bottom-up” proteomics on the same population of cells. Metabolic remodeling was observed upon histamine and corticosteroid treatment of the IL-13-exposed lung cell monolayers, in correlation with alterations in the proteomic profile. This proof of principle study demonstrates the utility of in vivo nano-DESI MS for characterizing ALI tissue layers, and the new markers identified in our study provide a good starting point for future, larger-scale studies.