Endoplasmic reticulum-targeting delivery of curcumin alters reactive oxygen species production and phenotypes in activated macrophages

Autor: Chia Liang Yen, Ru-Fen Chen, Dar-Bin Shieh, Si-Tse Jiang, Chi-Chang K Shieh
Rok vydání: 2020
Předmět:
Zdroj: The Journal of Immunology. 204:73.20-73.20
ISSN: 1550-6606
0022-1767
DOI: 10.4049/jimmunol.204.supp.73.20
Popis: Chronic granulomatous disease (CGD) is a primary immunodeficiency disease caused by defects in the leukocyte NADP oxidase. We previously reported that organelle-targeted delivery of sarcoplasmic/endoplasmic reticulum calcium pump (SERCA) inhibitor curcumin with the endoplasmic reticulum (ER)-targeting peptide decorated PLGA nanoparticles (NPs) rescues mutant H338Y-gp91phox protein maturation of a particular type of CGD with a CybbC1024T mutation, leading to ER retention of the mutant protein. However, how the rescuing of mutant H338Y-gp91 phox protein with ER-targeting curcumin-PLGA NPs on macrophages functions and differentiation are still unknown. In this study, we analyzed gp91phox maturation and macrophage M1/M2 polarization in bone marrow-derived macrophages (BMDMs) from wild-type (WT), Cybb−/−, and CybbC1024T transgenic Cybb−/−mice. First, we found that the levels of CD86 and CD206 expression with lipopolysaccharide+interferon-γ (LPS+IFN-γ) stimulation were similar in WT and CybbC1024T transgenic Cybb−/−BMDMs and CD206 expression was lowered in Cybb−/−mice when compared with WT and CybbC1024T transgenic Cybb−/−BMDMs. Second, we found that CD206 levels after LPS+IFN-γ stimulation were enhanced by free curcumin, curcumin-PLGA NPs and ER-targeting curcumin-PLGA NPs treatment in CybbC1024T transgenic Cybb−/−BMDMs, but not in WT and Cybb−/− BMDMs. Meanwhile, we found that ER-targeting curcumin-PLGA NPs enhanced gp91phox glycosylation in CybbC1024T transgenic Cybb−/−BMDMs. These findings may indicate that both the expression and maturation of gp91phox are crucial for macrophage M1/M2 polarization. Gp91phox maturation may be important for M2 phenotypes in activated macrophages.
Databáze: OpenAIRE
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