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

Journal Article · Wed Dec 15 04:00:00 EST 2021 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2021.112938· OSTI ID:23195270

Kobayashi, Ken; Matsunaga, Kota ^[1]; Tsugami, Yusaku ^[2]; Wakasa, Haruka; Nishimura, Takanori ^[1]

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1. Laboratory of Cell and Tissue Biology, Research Faculty of Agriculture, Hokkaido University, North 9, West 9, 060-8589, Sapporo (Japan)
2. Laboratory of Animal Histophysiology, Graduate School of Integrated Science for Life Faculty of Applied Biological Science, Hiroshima University, 1-4-4, Kagamiyama, Higashi-Hiroshima, 739-8528 (Japan)

Highlights: • TNF-α, IL-1β, and IL-6 directly affect tight junctions of MECs in different ways. • IL-1β rapidly disrupts tight junctions at tricellular contacts between MECs. • IL-1β decreases the amount of tight junction proteins and weaken the TJ barrier. • Activation of p38 by IL-1β triggers disruption of tight junctions. 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-1β, IL-6, or TNF-α. 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-α, IL-1β, and IL-6 affected lactation-specific TJs in different ways. In particular, upon activation of p38 and JNK signalling, IL-1β caused rapid disruption of TJs at tricellular contact points. IL-1β treatment led to decreased CLDN3, CLDN4, and OCLN levels and a weakened TJ barrier. The adverse effects of IL-1β 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-1β or anisomycin. These results indicate that IL-1β is a key cytokine that adversely affects the TJs between MECs by activating p38.

• OSTI ID: 23195270
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 2 Vol. 409; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
IN VITRO
INFLAMMATION
LACTATES
LACTATION
LYMPHOKINES
MAMMARY GLANDS
MILK