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Cranberry bioactives induce TLR signaling and promote a state of immune preparedness in THP‐1 monocytes/macrophages
Author(s) -
Creasy Rebecca A,
Khoo Christina,
Percival Susan S
Publication year - 2013
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.27.1_supplement.637.29
Subject(s) - thp1 cell line , innate immune system , immune system , cranberry juice , chemistry , receptor , monocyte , toll like receptor , cell culture , microbiology and biotechnology , biology , biochemistry , immunology , endocrinology , genetics , urinary system
Cranberries are a rich source of proanthocyanidins (PAC). Because of the unique structure of PAC, we hypothesized that cranberry interacts with pathogen recognition receptors on innate immune cells. Our objective was to evaluate Toll‐like receptor (TLR)‐4 PAC recognition and resulting changes in cytokine mRNA and protein. HEK‐Blue‐hTLR4 cells, containing inducible SEAP reporter genes, were treated with cranberry fractions, LPS, or vehicle. Cranberry fraction containing primarily PAC significantly increased SEAP activity in cell supernatant relative to vehicle. To determine if cranberry primes innate immune cells, THP‐1 cells were differentiated into macrophages and incubated with cranberry or vehicle. Cranberry treatment resulted in significantly higher MIP‐1α mRNA levels without TNFα and IL‐ 1β mRNA increases. An LPS challenge of cranberry‐treated macrophages induced a subtle increase in MIP‐1α protein secretion. In a second experiment, THP‐1 macrophages were treated with cranberry fractions, LPS, or DMSO, then treated with actinomycin D and harvested at times up to 3 hr. Cranberry treatment stabilized MIP‐1α transcripts to a greater extent than did LPS or vehicle. This data suggest that cranberry activates a TLR signaling pathway and primes THP‐1 cells for enhanced response to pathogen challenge via transcript stabilization. Funding provided by Ocean Spray Cranberries, Inc