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β‐Cryptoxanthin and Its Cleavage Metabolite, 3‐OH‐β‐Apo‐10′‐Carotenal, can Inhibit LPS‐induced Inflammatory Responses in Human Bronchial Epithelial Cells
Author(s) -
Hu KangQuan,
Mein Jonathan,
Wang XiangDong
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.603.1
Subject(s) - chemistry , phosphorylation , inflammation , metabolite , lipopolysaccharide , in vitro , pharmacology , cell culture , protein kinase b , sirtuin 1 , biochemistry , biology , immunology , downregulation and upregulation , gene , genetics
We have previously demonstrated that supplementation with the xanthophyll β‐cryptoxanthin (BCX)suppresses smoke/nicotine induced‐inflammation, emphysema, and lung tumorigenesis in animal models, which is likely to be independent of its provitamin A activity. These studies raised the question as to whether the protective effects of BCX result from the intact molecule or from its metabolites, independent of vitamin A. In the present study, we examined the effects of BCX and its cleavage metabolite by β‐carotene‐9′,10′‐oxygenase, 3‐OH‐β‐apo‐10′‐carotenal (3OH‐BA10C), against lipopolysaccharide (LPS)‐induced inflammatory responses of human bronchial epithelial cell line BEAS‐2B in vitro. Results showed that pre‐treatments of either BCX or 3OH‐BA10C in BEAS‐2B cells up‐regulated sirtuin 1 (SIRT1, a NAD+‐dependent protein deacetylase) protein expression and inhibited the LPS‐induced mRNA expressions of IL‐6 and TNF‐α in a dose‐dependent manner (1 to 4 μM concentrations). While these effects were associated with reduced AKT phosphorylation, BCX, not 3‐OH‐BA10C, up‐regulated IκB‐α (inhibitor of NF‐κB) protein without affecting its phosphorylation in BEAS‐2B cells. In contrast, 3OH‐BA10C induced the expression of hemo oxygenase‐1 (HO‐1) at both mRNA and protein levels in both dose‐ and time‐dependent manners. Taken together, these data demonstrate that both BCX and 3OH‐BA10C, at comparable doses, attenuate LPS‐induced inflammatory responses via differential molecular mechanisms, indicating thatthese biological activities could be due to action of their own molecule. Supported by the NIH grant CA176256