27-Hydroxycholesterol induces expression of zonula occludens-1 in monocytic cells via multiple kinases pathways.

Hyok-Rae Cho, Bo-Young Kim, Koanhoi Kim, Dongjun Lee, Seong-Kug Eo, Yonghae Son

Scientific reports 2022 May 17

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Zonula occludens (ZO)-1, a tight-junction protein (TJP), is expressed in dendritic cells (DCs) but not in monocytes, and 27-hydroxycholesterol (27OHChol) drives the differentiation of monocytes into DCs. Because the effects of 27OHChol on ZO-1 are not yet clearly defined, we investigated whether 27OHChol induces expression of the TJP. The treatment of human THP-1 monocytic cells with 27OHChol resulted in the elevated transcript levels of ZO-1 but not of ZO-2 or -3. 27OHChol increased the total amount of ZO-1 protein in the cells as well as its level on the cells surface. Cholesterol, however, did not influence expression of ZO-1. And, the expression of ZO-1 protein was mediated by endoplasmic reticulum (ER)-to-Golgi body transport system. Pharmacological kinase inhibition with LY294002 (a PI3K inhibitor), U0126 (a MEK/ERK inhibitor), or PP2 (a Src family kinase inhibitor) resulted in impaired ZO-1 expression at both transcript and protein levels. Drugs that are reported to suppress DC differentiation also inhibited 27OHChol-mediated expression and the localization of ZO-1, indicating the coincidence of ZO-1 upregulation and DC differentiation. These results suggest that ZO-1 is differentially expressed while monocytes differentiate into DCs in the presence of 27OHChol via pathways in which distinct signaling molecules are involved. © 2022. The Author(s).

Citation

Hyok-Rae Cho, Bo-Young Kim, Koanhoi Kim, Dongjun Lee, Seong-Kug Eo, Yonghae Son. 27-Hydroxycholesterol induces expression of zonula occludens-1 in monocytic cells via multiple kinases pathways. Scientific reports. 2022 May 17;12(1):8213