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Lactobacillus paracasei-derived extracellular vesicles attenuate the intestinal inflammatory response by augmenting the endoplasmic reticulum stress pathway

  • 2020-03
  • Experimental & Molecular Medicine 52(3)
    • J. Choi
    • C. Moon
    • Tae-Seop Shin
    • Eun Kyoung Kim
    • Andrea McDowell
    • Min-Kyung Jo
    • Y. Joo
    • Seong-Eun Kim
    • Hye-Kyung Jung
    • K. Shim
    • S. Jung
    • Yoon-Keun Kim

Abstract

Lactobacillus paracasei is a major probiotic and is well known for its anti-inflammatory properties. Thus, we investigated the effects of L. paracasei-derived extracellular vesicles (LpEVs) on LPS-induced inflammation in HT29 human colorectal cancer cells and dextran sulfate sodium (DSS)-induced colitis in C57BL/6 mice. ER stress inhibitors (salubrinal or 4-PBA) or CHOP siRNA were utilized to investigate the relationship between LpEV-induced endoplasmic reticulum (ER) stress and the inhibitory effect of LpEVs against LPS-induced inflammation. DSS (2%) was administered to male C57BL/6 mice to induce inflammatory bowel disease, and disease activity was measured by determining colon length, disease activity index, and survival ratio. In in vitro experiments, LpEVs reduced the expression of the LPS-induced pro-inflammatory cytokines IL-1α, IL-1β, IL-2, and TNFα and increased the expression of the anti-inflammatory cytokines IL-10 and TGFβ. LpEVs reduced LPS-induced inflammation in HT29 cells and decreased the activation of inflammation-associated proteins, such as COX-2, iNOS and NFκB, as well as nitric oxide. In in vivo mouse experiments, the oral administration of LpEVs also protected against DSS-induced colitis by reducing weight loss, maintaining colon length, and decreasing the disease activity index (DAI). In addition, LpEVs induced the expression of endoplasmic reticulum (ER) stress-associated proteins, while the inhibition of these proteins blocked the anti-inflammatory effects of LpEVs in LPS-treated HT29 cells, restoring the pro-inflammatory effects of LPS. This study found that LpEVs attenuate LPS-induced inflammation in the intestine through ER stress activation. Our results suggest that LpEVs have a significant effect in maintaining colorectal homeostasis in inflammation-mediated pathogenesis.

Research Insights

SupplementHealth OutcomeEffect TypeEffect Size
Lacticaseibacillus paracasei Lpc-37Improved Colitis SymptomsBeneficial
Large
Lacticaseibacillus paracasei Lpc-37Increased Anti-Inflammatory Cytokine LevelsBeneficial
Moderate
Lacticaseibacillus paracasei Lpc-37Reduced Intestinal InflammationBeneficial
Large
Lactobacillus paracasei DSM 13434Increased ER Stress-Associated ProteinsNeutral
Small
Lactobacillus paracasei DSM 13434Protection Against ColitisBeneficial
Large
Lactobacillus paracasei DSM 13434Reduced Intestinal InflammationBeneficial
Large
Lactobacillus paracasei HA-196Maintained Colorectal HomeostasisBeneficial
Large
Lactobacillus paracasei HA-196Protection Against ColitisBeneficial
Large
Lactobacillus paracasei HA-196Reduced Inflammatory Protein ActivationBeneficial
Moderate
Lactobacillus paracasei HA-196Reduced Inflammatory ResponseBeneficial
Large
Lactobacillus paracasei IMC 502Increased Anti-Inflammatory Cytokine LevelsBeneficial
Moderate
Lactobacillus paracasei IMC 502Reduced Colitis SymptomsBeneficial
Large
Lactobacillus paracasei IMC 502Reduced Intestinal InflammationBeneficial
Large
Lactobacillus paracasei LPC09Enhanced Endoplasmic Reticulum Stress ResponseBeneficial
Moderate
Lactobacillus paracasei LPC09Protection Against ColitisBeneficial
Large
Lactobacillus paracasei LPC09Reduced Inflammation LevelsBeneficial
Large
Lactobacillus paracasei UALpc-04Enhanced Colorectal HomeostasisBeneficial
Moderate
Lactobacillus paracasei UALpc-04Protection Against ColitisBeneficial
Large
Lactobacillus paracasei UALpc-04Reduced Inflammation LevelsBeneficial
Large
Lactobacillus paracasei UALpc-04Reduced LPS-Induced InflammationBeneficial
Moderate
Lactobacillus paracasei VPro 224Enhanced Endoplasmic Reticulum Stress ResponseBeneficial
Moderate
Lactobacillus paracasei VPro 224Reduced Inflammatory Protein ActivationBeneficial
Moderate
Lactobacillus paracasei VPro 224Reduced Pro-Inflammatory CytokinesBeneficial
Moderate
Lactobacillus paracasei VPro 224Reduced Weight LossBeneficial
Moderate
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