title: The procyanidin trimer C1 induces macrophage activation via NF-κB and MAPK pathways, leading to Th1 polarization in murine splenocytes.
abstract: Numerous studies have shown various relationships between foods with a high nutritional value and a robust immune response, particularly studies that have focused on host protection and cytokine networks. This study aimed to clarify the role played by the procyanidin trimer C1 in innate and adaptive immunity. Procyanidin C1 did not exert cytotoxicity at concentrations ranging from 7.8 to 62.5 μg/ml in macrophage cells; therefore, concentration of 62.5 μg/ml was used as the maximum dose of procyanidin C1 throughout subsequent experiments. Procyanidin C1 enhanced inducible nitric oxide synthase-mediated nitric oxide production in a concentration-dependent manner. In addition, procyanidin C1 functionally induced macrophage activation by augmenting the expression of cell surface molecules (CD80, CD86, and MHC II) and proinflammatory cytokine production (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6) via activation of mitogen-activated protein kinase (MAPK), e.g., p38, ERK, and JNK and nuclear factor (NF)-κB signaling pathways. Interestingly, procyanidin C1 effectively polarized T helper type 1 (Th1) by secreting Th1-mediated cytokines (interferon-γ, IL-12p70, and IL-2) and inducing splenocyte proliferation, indicating that procyanidin C1 contributes to Th1 polarization of the immune response. Accordingly, these findings confirms that the procyanidin C1 induces macrophage activation via NF-κB and MAPK pathways, leading to Th1 polarization in murine splenocytes, which suggests that procyanidin C1 regulates innate and adaptive immunity by macrophage activation and Th1 polarization.
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185, Republic of Korea.
authors.forename: Nak-Yun
authors.initials: NY
authors.lastname: Sung
authors.forename: Mi-So
authors.initials: MS
authors.lastname: Yang
authors.forename: Du-Sup
authors.initials: DS
authors.lastname: Song
authors.forename: Eui-Baek
authors.initials: EB
authors.lastname: Byun
authors.forename: Jae-Kyung
authors.initials: JK
authors.lastname: Kim
authors.forename: Jong-Heum
authors.initials: JH
authors.lastname: Park
authors.forename: Beom-Seok
authors.initials: BS
authors.lastname: Song
authors.forename: Ju-Woon
authors.initials: JW
authors.lastname: Lee
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Park
authors.forename: Hyun-Jin
authors.initials: HJ
authors.lastname: Park
authors.forename: Myung-Woo
authors.initials: MW
authors.lastname: Byun
authors.forename: Eui-Hong
authors.initials: EH
authors.lastname: Byun
authors.forename: Jae-Hun
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000818:Animals; D044946:Biflavonoids / Q000737:chemistry* / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology; D002392:Catechin / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D058105:Polymerization; D044945:Proanthocyanidins / Q000737:chemistry* / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology* / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects
chemical_list: D044946:Biflavonoids; D016207:Cytokines; D016328:NF-kappa B; D044945:Proanthocyanidins; D009569:Nitric Oxide; C479583:procyanidin C; D002392:Catechin
keywords: BMDMs; Bone marrow-derived macrophage; FBS; HRP; IFN; IL; IκB-α; MAPK; Murine splenocyte; NF-κB; NO; PVDF; Procyanidin C1; RAW 264.7 cells; RPMI; Roswell Park Memorial Institute; T helper type 1; T helper type 2; TNF; Th1; Th1 polarization; Th2; bone-marrowderived macrophages; fetal bovine serum; horseradish peroxidase; iNOS; inducible nitric oxide synthase; inhibitory κB-α; interferon; interleukin; mAb; mitogen-activated protein kinases; monoclonal Ab; nitric oxide; nuclear factor κB; pAb; polyclonal Ab; polyvinylidene difluoride; tumor necrosis factor