Immune response of human cultured cells towards macrocyclic Fe 2 PO and Fe 2 PC bioactive cyclophane complexes

PeerJ

article

Alex J. Salazar-Medina¹  Enrique F. Velazquez-Contreras²  Rocio Sugich-Miranda³  Hisila Santacruz¹  Rosa E. Navarro¹  Fernando Rocha-Alonzo³  Maria A. Islas-Osuna¹  Patricia L. Chen⁵  Sarah G.B. Christian⁵  Amelia A. Romoser⁶  Scott V. Dindot⁵  Christie M. Sayes⁷  Rogerio R. Sotelo-Mundo⁸  Michael F. Criscitiello⁵ 

[1] Cátedra CONACYT-Departamento de Investigación en Polímeros y Materiales, Universidad de Sonora;Departamento de Investigación en Polímeros y Materiales, Universidad de Sonora;Departamento de Ciencias Químico Biológicas, Universidad de Sonora;Centro de Investigación en Alimentación y Desarrollo;Comparative Immunogenetics Laboratory, Department of Veterinary Pathobiology, Texas A&M University, College Station;Department of Veterinary Pathobiology, Texas A&M University, College Station;Nanotoxicology and Nanopharmacology, RTI International, Research Triangle;Biomolecular Structure Laboratory

关键词: Iron;    Gene expression;    Antioxidant;    IRAK;    Cyclophanes;    CD14;    Biomimetic;    Interleukin 1;   

DOI  :  10.7717/peerj.8956

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

Synthetic molecules that mimic the function of natural enzymes or molecules have untapped potential for use in the next generation of drugs. Cyclic compounds that contain aromatic rings are macrocyclic cyclophanes, and when they coordinate iron ions are of particular interest due to their antioxidant and biomimetic properties. However, little is known about the molecular responses at the cellular level. This study aims to evaluate the changes in immune gene expression in human cells exposed to the cyclophanes Fe2PO and Fe2PC. Confluent human embryonic kidney cells were exposed to either the cyclophane Fe2PO or Fe2PC before extraction of RNA. The expression of a panel of innate and adaptive immune genes was analyzed by quantitative real-time PCR. Evidence was found for an inflammatory response elicited by the cyclophane exposures. After 8 h of exposure, the cells increased the relative expression of inflammatory mediators such as interleukin 1; IRAK, which transduces signals between interleukin 1 receptors and the NFκB pathway; and the LPS pattern recognition receptor CD14. After 24 h of exposure, regulatory genes begin to counter the inflammation, as some genes involved in oxidative stress, apoptosis and non-inflammatory immune responses come into play. Both Fe2PO and Fe2PC induced similar immunogenetic changes in transcription profiles, but equal molar doses of Fe2PC resulted in more robust responses. These data suggest that further work in whole animal models may provide more insights into the extent of systemic physiological changes induced by these cyclophanes.

【 授权许可】

CC BY