Abstract
COPD is a prevalent lung disease with significant impacts on public health. Affected airways exhibit pulmonary neutrophilia and consequent secretion of pro-inflammatory cytokines and proteases, which result in lung emphysema. Probiotics act as nonspecific modulators of the innate immune system that improve several inflammatory responses. To investigate the effect of Lactobacillus rhamnosus (Lr) on cigarette smoke (CS)-induced COPD C57Bl/6 mice were treated with Lr during the week before COPD induction and three times/week until euthanasia. For in vitro assays, murine bronchial epithelial cells as well as human bronchial epithelial cells exposed to cigarette smoke extract during 24 hours were treated with Lr 1 hour before CSE addition. Lr treatment attenuated the inflammatory response both in the airways and lung parenchyma, reducing inflammatory cells infiltration and the production of pro-inflammatory cytokines and chemokines. Also, Lr-treated mice presented with lower metalloproteases in lung tissue and lung remodeling. In parallel to the reduction in the expression of TLR2, TLR4, TLR9, STAT3, and NF-κB in lung tissue, Lr increased the levels of IL-10 as well as SOCS3 and TIMP1/2, indicating the induction of an anti-inflammatory environment. Similarly, murine bronchial epithelial cells as well as human bronchial epithelial cells (BEAS) exposed to CSE produced pro-inflammatory cytokines and chemokines, which were inhibited by Lr treatment in association with the production of anti-inflammatory molecules. Moreover, the presence of Lr also modulated the expression of COPD-associated transcription found into BALF of COPD mice group, i.e., Lr downregulated expression of NF-κB and STAT3, and inversely upregulated increased expression of SOCS3. Thus, our findings indicate that Lr modulates the balance between pro- and anti-inflammatory cytokines in human bronchial epithelial cells upon CS exposure and it can be a useful tool to improve the lung inflammatory response associated with COPD.
Highlights
Chronic obstructive pulmonary disease (COPD) is one of the major chronic health conditions in which disability and death rates are increasing worldwide, the development of new strategies to disease management remains underwhelming [1,2,3]
In concordance with the characteristic inflammatory response observed in chronic obstructive pulmonary disease (COPD) manifestation, the infiltrating cells were constituted by macrophages (2B), neutrophils (2C), and lymphocytes (2D)
The Lactobacillus rhamnosus (Lr) group presented with a significant reduction in the levels of both pro-inflammatory cytokines and chemokines when compared with the COPD mice
Summary
Chronic obstructive pulmonary disease (COPD) is one of the major chronic health conditions in which disability and death rates are increasing worldwide, the development of new strategies to disease management remains underwhelming [1,2,3]. The intrinsic factors that contribute to COPD development remais subject of discussion, the cigarette smoke is well recognized as a risk factor for the disease [3]. Chemokines such as CXCL1 and CXCL8 as well as cytokines TNF, IL-1β, IL-6, and IL-17 are chemotactic factors that attract inflammatory cells to the injured lung, principally neutrophils and monocyte-derived macrophage [4,5,6,7], where the pulmonary destruction initiates, compromising the alveolar parenchyma [8]. During the pathogenesis of COPD, the balance between the effects of MMP and its TIMP is dysregulated [16,17,18], since that MMP released by neutrophils overlaps with TIMP activity with consequent pulmonary tissue destruction
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