Cyclosporin A inhibits differentiation and activation of monocytic cells induced by 27-hydroxycholesterol

• Published in: International immunopharmacology 2019-04, Vol.69, p.358-367
• Main Authors: Son, Yonghae, Choi, Jeongyoon, Kim, Boyoung, Park, Young Chul, Eo, Seong-Kug, Cho, Hyok-rae, Bae, Sun Sik, Kim, Chi Dae, Kim, Koanhoi
• Format: Article
• Language: English
• Subjects: 27-hydroxycholesterol; Biological effects; CD14 antigen; CD80 antigen; CD83 antigen; Cell activation; Cholesterol; Cyclosporin A; Dendritic cell; Dendritic cells; Differentiation; Gelatinase B; Homing; Human behavior; Immune response; Immune system; Innate immunity; M1 polarization; Macrophages; Major histocompatibility complex; Markers; Monocyte chemoattractant protein 1; Monocytes; Polarization; Transcription
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2019.01.045

27-Hydroxycholesterol (27OHChol) is a bioactive molecule that induces monocytic cell activation and differentiation and thereby participates in immune responses under hypercholesterolemic condition. However, it is unknown whether cyclosporin A (CsA), an immunosuppressant, affects biological effects of 27OHChol. In this study, we investigated whether CsA alters 27OHChol-induced cellular and molecular responses using the human monocyte/macrophage THP-1 cells. Treatment of the cells with CsA resulted in decreased expression of the mDC-specific markers (CD80, CD83 and CD88) induced by 27OHChol. Reduced endocytic activity recovered in the presence of CsA. The drug also inhibited the expressions of MHC class I and II molecules and CD197, a homing molecule of mDCs. We further investigated the outcomes of CsA treatment on the expression of M1 polarization markers and CD14, a component of the innate immune system. The drug decreased transcript levels of genes associated with the M1 polarization of monocytic cells, including CCL2, as well as expression of CD14 and MMP-9 which is involved in soluble CD14 shedding. Taken together, these results indicate that CsA inhibits the 27OHChol-induced differentiation and activation of monocytic cells into a mature dendritic cell (mDC) type and an immuno-stimulatory M1 subset, respectively, thereby modifying immune responses in a milieu rich in cholesterol and oxidized cholesterol molecules. •Cyclosporine A (CsA) inhibits morphological and physiological changes of monocytic cells induced by 27OHChol.•CsA inhibits the production of inflammatory chemokines and MMP-9 induced by 27OHChol.•CsA inhibits the M1 polarization of monocytic cells induced by 27OHChol.