TY - JOUR
T1 - Changes in intestinal homeostasis and immunity in a cigarette smoke- and LPS-induced murine model for COPD
T2 - the lung-gut axis
AU - Wang, Lei
AU - Pelgrim, Charlotte E
AU - Peralta Marzal, Lucía N
AU - Korver, Stephanie
AU - van Ark, Ingrid
AU - Leusink-Muis, Thea
AU - van Helvoort, Ardy
AU - Keshavarian, Ali
AU - Kraneveld, Aletta D
AU - Garssen, Johan
AU - Henricks, Paul A J
AU - Folkerts, Gert
AU - Braber, Saskia
N1 - Funding Information:
We acknowledge the support of Xi Wan from the Novogene (UK) Company Limited.
Publisher Copyright:
Copyright © 2022 The Authors.
PY - 2022/9
Y1 - 2022/9
N2 - Chronic obstructive pulmonary disease (COPD) is often associated with intestinal comorbidities. In this study, changes in intestinal homeostasis and immunity in a cigarette smoke and lipopolysaccharide (LPS)-induced COPD model were investigated. Mice were exposed to cigarette smoke or air for 72 days, except days 42, 52 and 62 on which the mice were treated with saline or LPS via intratracheal instillation. Cigarette smoke exposure increased the airway inflammatory cell numbers, mucus production and different inflammatory mediators, including C-reactive protein (CRP) and keratinocyte-derived chemokine (KC), in bronchoalveolar lavage (BAL) fluid and serum. LPS did not further impact airway inflammatory cell numbers or mucus production but decreased inflammatory mediators levels in BAL fluid. T helper (Th) 1 cells were enhanced in the spleen after cigarette smoke exposure, however, in combination with LPS caused an increase in Th1 and Th2 cells. Histomorphological changes were observed in the proximal small intestine after cigarette smoke exposure and addition of LPS had no effect. Cigarette smoke activated the intestinal immune network for IgA production in the distal small intestine which was associated with increased fecal sIgA levels and enlargement of Peyer's patches. Cigarette smoke plus LPS decreased fecal sIgA levels and the size of Peyer's patches. In conclusion, cigarette smoke with or without LPS affects intestinal health as observed by changes in intestinal histomorphology and immune network for IgA production. Elevated systemic mediators might play a role in the lung-gut crosstalk. These findings contribute to a better understanding of intestinal disorders related to COPD.
AB - Chronic obstructive pulmonary disease (COPD) is often associated with intestinal comorbidities. In this study, changes in intestinal homeostasis and immunity in a cigarette smoke and lipopolysaccharide (LPS)-induced COPD model were investigated. Mice were exposed to cigarette smoke or air for 72 days, except days 42, 52 and 62 on which the mice were treated with saline or LPS via intratracheal instillation. Cigarette smoke exposure increased the airway inflammatory cell numbers, mucus production and different inflammatory mediators, including C-reactive protein (CRP) and keratinocyte-derived chemokine (KC), in bronchoalveolar lavage (BAL) fluid and serum. LPS did not further impact airway inflammatory cell numbers or mucus production but decreased inflammatory mediators levels in BAL fluid. T helper (Th) 1 cells were enhanced in the spleen after cigarette smoke exposure, however, in combination with LPS caused an increase in Th1 and Th2 cells. Histomorphological changes were observed in the proximal small intestine after cigarette smoke exposure and addition of LPS had no effect. Cigarette smoke activated the intestinal immune network for IgA production in the distal small intestine which was associated with increased fecal sIgA levels and enlargement of Peyer's patches. Cigarette smoke plus LPS decreased fecal sIgA levels and the size of Peyer's patches. In conclusion, cigarette smoke with or without LPS affects intestinal health as observed by changes in intestinal histomorphology and immune network for IgA production. Elevated systemic mediators might play a role in the lung-gut crosstalk. These findings contribute to a better understanding of intestinal disorders related to COPD.
U2 - 10.1152/ajplung.00486.2021
DO - 10.1152/ajplung.00486.2021
M3 - Article
C2 - 35699290
SN - 1040-0605
VL - 323
SP - L266-L280
JO - American Journal of Physiology-Lung Cellular and Molecular Physiology
JF - American Journal of Physiology-Lung Cellular and Molecular Physiology
IS - 3
ER -