Search

Atopic dermatitis (AD) skin is characterized by over-expression of interleukin (IL)-4, IL-13 and IL-25. When methyl-β-cyclodextrin (MβCD) treatment preceded exposure to these interleukins, combination of both treatments was found to mimic hallmarks of AD in vitro, such as barrier weakening, histological alterations and typical signaling responses in a reconstructed human epidermis (RHE). However, the respective role of each IL and whether any of them is critical when combined with MβCD treatment was unknown. Therefore, this work aimed to distinguish RHE responses after exposure to MβCD and each one of the three IL reported to mimic typical features of AD. IL-4 incubation preceded by MβCD was found responsible for altered histology, as well as for barrier alterations, evidenced by electrical resistance and dye permeation measurements. This combination further decreased loricrin (LOR) immunoreactivity, whereas mainly IL-25, combined to MβCD treatment, was able to downregulate filaggrin (FLG) mRNA level. Carbonic anhydrase II (CA2) and hyaluronan synthase 3 (HAS3), two other markers up-regulated in AD, were also induced when MβCD treatment was followed by IL-4, whilst the expression of neural epidermal growth factor-like 2 (NELL2) was up-regulated by paired IL-4 and IL-13. In conclusion, multiple features of AD were found in this in vitro model mainly when treatment of RHE by IL-4 was conducted after preliminary MβCD incubation. [ABSTRACT FROM AUTHOR]

Breast cancer remains a research priority due to its invasive phenotype. Although the role of ion channels in cancer is now well established, the role of inositol (1,4,5)-trisphosphate (IP 3 ) receptors (IP 3 Rs) remains enigmatic. If the three IP 3 Rs subtypes expression have been identified in various cancers, little is known about their physiological role. Here, we investigated the involvement of IP 3 R type 3 (IP 3 R 3 ) in the migration processes of three human breast cancer cell lines showing different migration velocities: the low-migrating MCF-7 and the highly migrating and invasive MDA-MB-231 and MDA-MB-435S cell lines. We show that a higher IP 3 R3 expression level, but not IP 3 R1 nor IP 3 R2, is correlated to a stronger cell line migration capacity and a sustained calcium signal. Interestingly, silencing of IP 3 R3 highlights an oscillating calcium signaling profile and leads to a significant decrease of cell migration capacities of the three breast cancer cell lines. Conversely, stable overexpression of IP 3 R3 in MCF-7 cells significantly increases their migration capacities. This effect is completely reversed by IP 3 R3 silencing. In conclusion, we demonstrate that IP 3 R3 expression level increases the migration capacity of human breast cancer cells by changing the calcium signature., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no interest of any kind affecting this study.