Lactobacillus acidophilus KLDS 1.0738 inhibits TLR4/NF-κB inflammatory pathway in β-lactoglobulin-induced macrophages via modulating miR-146a.

Our previous study has confirmed that Lactobacillus acidophilus KLDS 1.0738 (La KLDS 1.0738) could alleviate β-lactoglobulin (β-Lg)-induced allergic inflammation. This study further explored its molecular regulation mechanism through an in vitro macrophage model. β-Lg-induced macrophages were treated with strains of viable or non-viable L. acidophilus and Toll-like receptor 4 (TLR4) inhibitor or miR-146a inhibitor. Our results revealed that β-Lg stimulation led to the increased expression of TLR4/NF-κB signal pathway in macrophages. Similar to TLR4 inhibitor treatment, La KLDS 1.0738 interventions significantly reduced the allergic inflammation by inhibition of TLR4 pathway, which was superior to the commercial L. acidophilus GMNL-185 strains (La GMNL-185) or the control, especially in living L. acidophilus-treated group. Furthermore, La KLDS 1.0738 strains could remarkably reduce transduction of TLR4 and inflammatory cytokine production, which was closely associated with up-regulation of miR-146a levels. MiR-146a inhibitor attenuated the alleviative effect of La KLDS 1.0738, indicating miR-146a might be a crucial mediator of L. acidophilus strains to reduce β-Lg-induced inflammation in macrophages through TLR4 pathway. In conclusion, these observations highlighted that probiotics might regulate host miRNA levels to down-regulate TLR4/NF-κB-dependent inflammation. PRACTICAL APPLICATIONS: Cow's milk allergy (CMA) is one of the most common diseases of food allergy, which has a high prevalence in infants and young children. La KLDS 1.0738 has been shown to be effective in alleviating β-Lg-induced allergic inflammation. Our study further found that treatment with La KLDS 1.0738 could suppress the TLR4/NF-κB signaling pathway via modulating miR-146a expression, thereby reducing the overexpression of downstream inflammatory factors. This study not only elucidates the specific pathway of La KLDS 1.0738 to relieve allergic inflammation, but also provides a new insight into the molecular mechanism for the remission and treatment of CMA by probiotics.