Lacticaseibacillus Rhamnosus Modulates the Inflammatory Response and the Subsequent Lung Damage in a Murine Model of Acute Lung Inflammation

Overview

Journal Clinics (Sao Paulo)

Publisher Elsevier

Specialty General Medicine

Date 2022 Mar 18

PMID 35303586

Authors

Fabiana Olimpio

Jose Roberto Mateus da Silva

Rodolfo P Vieira

Carlos R Oliveira

Flavio Aimbire

Affiliations

Soon will be listed here.

Abstract

Objective: The present study investigated the anti-inflammatory effect of the probiotic Lacticaseibacillus rhamnosus (Lr) on lung inflammation induced by Lipopolysaccharide (LPS) of Escherichia coli in C57BL/6 mice.

Methods: C57BL/6 mice were divided into four groups: control, LPS, Lr (1 day) + LPS, and Lr (14 days) + LPS. Total and differential cells from Bronchoalveolar Lavage Fluid (BALF) were counted in a Neubauer 40X chamber, and pro-and anti-inflammatory cytokines (IL-1β, IL-6, CXCL-1, TNF-α, TGF-β, and IL-10) were measured by ELISA assay. The analysis of whole leukocytes in blood was performed using the automated system Sysmex 800i. Morphometry of pulmonary tissue evaluated alveolar hemorrhage, alveolar collapse, and inflammatory cells. Pulmonary vascular permeability was assessed by Evans blue dye extravasation, and bronchoconstriction was evaluated in a tissue bath station. The transcription factor NF-kB was evaluated by ELISA, and its gene expression and TLR-2, TLR-4, MMP-9, MMP-12, and TIMP by PCR.

Results: The probiotic Lr had a protective effect against the inflammatory responses induced by LPS. Lr significantly reduced pro-inflammatory cells in the airways, lung parenchyma, and blood leukocytes. Furthermore, Lr reduced the production of pro-inflammatory cytokines and chemokines in BALF and the expression of TLRs, MMPs, and NF-kB in lung tissue and maintained the expression of TIMP in treated animals promoting a protective effect on lung tissue.

Conclusions: The results of the study indicate that pre-treatment with the probiotic Lr may be a promising way to mitigate lung inflammation in endotoxemia.

Citing Articles

The Microbiota-Gut-Brain Axis: Key Mechanisms Driving Glymphopathy and Cerebral Small Vessel Disease.

Che Mohd Nassir C, Che Ramli M, Ghazali M, Jaffer U, Abdul Hamid H, Mehat M Life (Basel). 2025; 15(1).

PMID: 39859943 PMC: 11766513. DOI: 10.3390/life15010003.

Dual Functioned Hexapeptide-Coated Lipid-Core Nanomicelles Suppress Toll-Like Receptor-Mediated Inflammatory Responses through Endotoxin Scavenging and Endosomal pH Modulation.

Ji Y, Sun L, Liu Y, Li Y, Li T, Gong J Adv Sci (Weinh). 2023; 10(19):e2301230.

PMID: 37078808 PMC: 10323664. DOI: 10.1002/advs.202301230.

References

Hakonarson H, Maskeri N, Carter C, Grunstein M . Regulation of TH1- and TH2-type cytokine expression and action in atopic asthmatic sensitized airway smooth muscle. J Clin Invest. 1999; 103(7):1077-87. PMC: 408262. DOI: 10.1172/JCI5809. View

Wu C, Chen P, Lee Y, Ko J, Lue K . Effects of immunomodulatory supplementation with Lactobacillus rhamnosus on airway inflammation in a mouse asthma model. J Microbiol Immunol Infect. 2014; 49(5):625-635. DOI: 10.1016/j.jmii.2014.08.001. View

Zocco M, Zileri Dal Verme L, Cremonini F, Piscaglia A, Nista E, Candelli M . Efficacy of Lactobacillus GG in maintaining remission of ulcerative colitis. Aliment Pharmacol Ther. 2006; 23(11):1567-74. DOI: 10.1111/j.1365-2036.2006.02927.x. View

Wang J, Li R, Peng Z, Hu B, Rao X, Li J . HMGB1 participates in LPS‑induced acute lung injury by activating the AIM2 inflammasome in macrophages and inducing polarization of M1 macrophages via TLR2, TLR4, and RAGE/NF‑κB signaling pathways. Int J Mol Med. 2019; 45(1):61-80. PMC: 6889921. DOI: 10.3892/ijmm.2019.4402. View

Aschner Y, Zemans R, Yamashita C, Downey G . Matrix metalloproteinases and protein tyrosine kinases: potential novel targets in acute lung injury and ARDS. Chest. 2014; 146(4):1081-1091. PMC: 4188143. DOI: 10.1378/chest.14-0397. View

Gao H, Xiao D, Gao L, Li X . MicroRNA‑93 contributes to the suppression of lung inflammatory responses in LPS‑induced acute lung injury in mice via the TLR4/MyD88/NF‑κB signaling pathway. Int J Mol Med. 2020; 46(2):561-570. PMC: 7307825. DOI: 10.3892/ijmm.2020.4610. View

Li L, Dong L, Zhao D, Gao F, Yan J . Classical dendritic cells regulate acute lung inflammation and injury in mice with lipopolysaccharide‑induced acute respiratory distress syndrome. Int J Mol Med. 2019; 44(2):617-629. PMC: 6605708. DOI: 10.3892/ijmm.2019.4208. View

Bagheri Y, Babaha F, Falak R, Yazdani R, Azizi G, Sadri M . IL-10 induces TGF-β secretion, TGF-β receptor II upregulation, and IgA secretion in B cells. Eur Cytokine Netw. 2020; 30(3):107-113. DOI: 10.1684/ecn.2019.0434. View

Wang Y, Gao L, Yang Z, Chen F, Zhang Y . Effects of probiotics on ghrelin and lungs in children with acute lung injury: A double-blind randomized, controlled trial. Pediatr Pulmonol. 2017; 53(2):197-203. DOI: 10.1002/ppul.23922. View

10.

Englert J, Bobba C, Baron R . Integrating molecular pathogenesis and clinical translation in sepsis-induced acute respiratory distress syndrome. JCI Insight. 2019; 4(2). PMC: 6413834. DOI: 10.1172/jci.insight.124061. View

11.

Wesley Alberca-Custodio R, Greiffo F, MacKenzie B, Oliveira-Junior M, Andrade-Sousa A, Graudenz G . Aerobic Exercise Reduces Asthma Phenotype by Modulation of the Leukotriene Pathway. Front Immunol. 2016; 7:237. PMC: 4905963. DOI: 10.3389/fimmu.2016.00237. View

12.

Budden K, Gellatly S, Wood D, Cooper M, Morrison M, Hugenholtz P . Emerging pathogenic links between microbiota and the gut-lung axis. Nat Rev Microbiol. 2016; 15(1):55-63. DOI: 10.1038/nrmicro.2016.142. View

13.

Inui T, Watanabe M, Nakamoto K, Sada M, Hirata A, Nakamura M . Bronchial epithelial cells produce CXCL1 in response to LPS and TNFα: A potential role in the pathogenesis of COPD. Exp Lung Res. 2019; 44(7):323-331. DOI: 10.1080/01902148.2018.1520936. View

14.

Zarbock A, Distasi M, Smith E, Sanders J, Kronke G, Harry B . Improved survival and reduced vascular permeability by eliminating or blocking 12/15-lipoxygenase in mouse models of acute lung injury (ALI). J Immunol. 2009; 183(7):4715-22. PMC: 2753988. DOI: 10.4049/jimmunol.0802592. View

15.

Zhang Y, Adner M, Cardell L . IL-1beta-induced transcriptional up-regulation of bradykinin B1 and B2 receptors in murine airways. Am J Respir Cell Mol Biol. 2007; 36(6):697-705. DOI: 10.1165/rcmb.2005-0369OC. View

16.

Byrne K, Cooper K, Carey P, Berlin A, Sielaff T, Blocher C . Pulmonary compliance: early assessment of evolving lung injury after onset of sepsis. J Appl Physiol (1985). 1990; 69(6):2290-5. DOI: 10.1152/jappl.1990.69.6.2290. View

17.

Liu W, Li C, Lu X, Bo L, Jin F . Overexpression of transcription factor EB regulates mitochondrial autophagy to protect lipopolysaccharide-induced acute lung injury. Chin Med J (Engl). 2019; 132(11):1298-1304. PMC: 6629347. DOI: 10.1097/CM9.0000000000000243. View

18.

Plaza-Diaz J, Ruiz-Ojeda F, Gil-Campos M, Gil A . Mechanisms of Action of Probiotics. Adv Nutr. 2019; 10(suppl_1):S49-S66. PMC: 6363529. DOI: 10.1093/advances/nmy063. View

19.

Fukuda S, Akiyama M, Harada H, Nakahama K . Effect of gap junction-mediated intercellular communication on TGF-β induced epithelial-to-mesenchymal transition. Biochem Biophys Res Commun. 2018; 508(3):928-933. DOI: 10.1016/j.bbrc.2018.12.027. View

20.

Zeng J, Wang C, Zhang F, Qi F, Wang S, Ma S . Effect of probiotics on the incidence of ventilator-associated pneumonia in critically ill patients: a randomized controlled multicenter trial. Intensive Care Med. 2016; 42(6):1018-28. DOI: 10.1007/s00134-016-4303-x. View