Oral feeding with probiotic Lactobacillus rhamnosus attenuates cigarette smoke-induced COPD in C57Bl/6 mice: Relevance to inflammatory markers in human bronchial epithelial cells

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 proinflammatory 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.

Photobiomodulation Therapy Restores IL-10 Secretion in a Murine Model of Chronic Asthma: Relevance to the Population of CD4+CD25+Foxp3+ Cells in Lung

“…In this scenario, it is important to draw our attention to the fact that even in mice from the Basal group, IL-10 levels vary a lot, and thus it is possible to find values of IL-10 a little bit higher than those found in most studies. In fact, diverse authors have also found values higher than 50 pg/ml in BALF of mice from the Basal group (33)(34)(35)(36). Our results are in accordance with findings in which IL-10 level in BALF of the Basal group reached 1,500 pg/ml (37).…”

The Beneficial Role of Probiotic Lactobacillus in Respiratory Diseases

“…In vitro experiment has demonstrated that L. rhamnosus NutRes1 can reduce inflammatory mediators produced by cigarette-activated human macrophages ( 124 ). Moreover, oral feeding of L. rhamnosus (strain not shown) increases levels of IL-10 as well as SOCS3 and TIMP1/2, and attenuates lung injury of COPD induced by cigarette in C57BL/6 mice ( 21 ). Additionally, the development of COPD is associated with reduction of Lactobacillus spp.…”

“…Meanwhile, emerging evidence shows that Lactobacillus can also modulate respiratory immunity ( 13 – 16 ). Administration of Lactobacillus confer a beneficial role in respiratory diseases including respiratory tract infections (RTIs), asthma, lung cancer, cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) ( 17 – 21 ). Administration of Lactobacillus may be an alternative strategy to alleviate respiratory diseases.…”

The Lactobacillus as a Probiotic: Focusing on Liver Diseases

“…In the COPD group, which was orally administered L. rhamnosus three times per week, the influx of inflammatory cells into the airways was inhibited compared to that in the COPD group that did not receive L. rhamnosus. It was involved with various immune responses [44].…”