IL-1β is a key inflammatory cytokine that weakens lactation-specific tight junctions of mammary epithelial cells

In lactating mammary glands, alveolar mammary epithelial cells (MECs) produce milk and form less-permeable tight junctions (TJs). However, alveolar TJs are weakened with a reduction in milk production in mammary glands due to mastitis or weaning in the presence of high levels of IL-1 beta, IL-6, or TNF-alpha. In this study, using in vitro cultured model of MECs with milk-producing ability and lactation-specific TJs, we investigated whether the aforementioned cytokines affect MEC TJs. The results showed that TNF-alpha, IL-1 beta, and IL-6 affected lactation-specific TJs in different ways. In particular, upon activation of p38 and JNK signalling, IL-1 beta caused rapid disruption of TJs at tricellular contact points. IL-1 beta treatment led to decreased CLDN3, CLDN4, and OCLN levels and a weakened TJ barrier. The adverse effects of IL-1 beta on TJs were mimicked by anisomycin, which is an activator of p38 and JNK signalling, and were blocked by MEC pretreatment with a p38 inhibitor but not a JNK inhibitor. The mislocalization of tricellulin at tricellular contact areas was confirmed in MECs treated with IL-1 beta or anisomycin. These results indicate that IL-1 beta is a key cytokine that adversely affects the TJs between MECs by activating p38.

Automated summary

This study found that IL-1 beta disrupts TJs between MECs by activating the p38 signaling pathway, leading to decreased levels of CLDN3, CLDN4, and OCLN and a weakened TJ barrier.