Immune response of human cultured cells towards macrocyclic Fe2PO and Fe2PC bioactive cyclophane complexes
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 antioxidan...
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doaj-df8ffdefcfe6421d85f05935675e7e2a2020-11-25T02:32:38ZengPeerJ Inc.PeerJ2167-83592020-04-018e895610.7717/peerj.8956Immune response of human cultured cells towards macrocyclic Fe2PO and Fe2PC bioactive cyclophane complexesAlex J. Salazar-Medina0Enrique F. Velazquez-Contreras1Rocio Sugich-Miranda2Hisila Santacruz3Rosa E. Navarro4Fernando Rocha-Alonzo5Maria A. Islas-Osuna6Patricia L. Chen7Sarah G.B. Christian8Amelia A. Romoser9Scott V. Dindot10Christie M. Sayes11Rogerio R. Sotelo-Mundo12Michael F. Criscitiello13Cátedra CONACYT-Departamento de Investigación en Polímeros y Materiales, Universidad de Sonora, Hermosillo, Sonora, MexicoDepartamento de Investigación en Polímeros y Materiales, Universidad de Sonora, Hermosillo, Sonora, MexicoDepartamento de Ciencias Químico Biológicas, Universidad de Sonora, Hermosillo, Sonora, MexicoDepartamento de Investigación en Polímeros y Materiales, Universidad de Sonora, Hermosillo, Sonora, MexicoDepartamento de Investigación en Polímeros y Materiales, Universidad de Sonora, Hermosillo, Sonora, MexicoDepartamento de Ciencias Químico Biológicas, Universidad de Sonora, Hermosillo, Sonora, MexicoDepartamento de Investigación en Polímeros y Materiales, Universidad de Sonora, Hermosillo, Sonora, MexicoComparative Immunogenetics Laboratory, Department of Veterinary Pathobiology, Texas A&M University, College Station, TX, USAComparative Immunogenetics Laboratory, Department of Veterinary Pathobiology, Texas A&M University, College Station, TX, USADepartment of Veterinary Pathobiology, Texas A&M University, College Station, TX, USADepartment of Veterinary Pathobiology, Texas A&M University, College Station, TX, USANanotoxicology and Nanopharmacology, RTI International, Research Triangle, MC, USABiomolecular Structure Laboratory, Centro de Investigación en Alimentación y Desarrollo, A.C., Hermosillo, Sonora, MexicoComparative Immunogenetics Laboratory, Department of Veterinary Pathobiology, Texas A&M University, College Station, TX, USASynthetic 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.https://peerj.com/articles/8956.pdfIronGene expressionAntioxidantIRAKCyclophanesCD14 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Alex J. Salazar-Medina Enrique F. Velazquez-Contreras Rocio Sugich-Miranda Hisila Santacruz Rosa E. Navarro Fernando Rocha-Alonzo Maria A. Islas-Osuna Patricia L. Chen Sarah G.B. Christian Amelia A. Romoser Scott V. Dindot Christie M. Sayes Rogerio R. Sotelo-Mundo Michael F. Criscitiello |
spellingShingle |
Alex J. Salazar-Medina Enrique F. Velazquez-Contreras Rocio Sugich-Miranda Hisila Santacruz Rosa E. Navarro Fernando Rocha-Alonzo Maria A. Islas-Osuna Patricia L. Chen Sarah G.B. Christian Amelia A. Romoser Scott V. Dindot Christie M. Sayes Rogerio R. Sotelo-Mundo Michael F. Criscitiello Immune response of human cultured cells towards macrocyclic Fe2PO and Fe2PC bioactive cyclophane complexes PeerJ Iron Gene expression Antioxidant IRAK Cyclophanes CD14 |
author_facet |
Alex J. Salazar-Medina Enrique F. Velazquez-Contreras Rocio Sugich-Miranda Hisila Santacruz Rosa E. Navarro Fernando Rocha-Alonzo Maria A. Islas-Osuna Patricia L. Chen Sarah G.B. Christian Amelia A. Romoser Scott V. Dindot Christie M. Sayes Rogerio R. Sotelo-Mundo Michael F. Criscitiello |
author_sort |
Alex J. Salazar-Medina |
title |
Immune response of human cultured cells towards macrocyclic Fe2PO and Fe2PC bioactive cyclophane complexes |
title_short |
Immune response of human cultured cells towards macrocyclic Fe2PO and Fe2PC bioactive cyclophane complexes |
title_full |
Immune response of human cultured cells towards macrocyclic Fe2PO and Fe2PC bioactive cyclophane complexes |
title_fullStr |
Immune response of human cultured cells towards macrocyclic Fe2PO and Fe2PC bioactive cyclophane complexes |
title_full_unstemmed |
Immune response of human cultured cells towards macrocyclic Fe2PO and Fe2PC bioactive cyclophane complexes |
title_sort |
immune response of human cultured cells towards macrocyclic fe2po and fe2pc bioactive cyclophane complexes |
publisher |
PeerJ Inc. |
series |
PeerJ |
issn |
2167-8359 |
publishDate |
2020-04-01 |
description |
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. |
topic |
Iron Gene expression Antioxidant IRAK Cyclophanes CD14 |
url |
https://peerj.com/articles/8956.pdf |
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