title: Quercetin supplementation suppresses the secretion of pro-inflammatory cytokines in the lungs of Mongolian gerbils and in A549 cells exposed to benzo[a]pyrene alone or in combination with β-carotene: in vivo and ex vivo studies.
abstract: In vitro studies have shown that quercetin modulates the effects of β-carotene induced by stimulants. Whether these reactions happen in vivo, however, is unclear. Thus, we investigated whether quercetin supplementation suppresses the harmful effects of benzo[a]pyrene (BaP) alone or combined with β-carotene in the lungs of Mongolian gerbils. The gerbils were given quercetin (100 mg/kg body wt, 3 times/week), β-carotene (10 mg/kg body wt, 3 times/week), and BaP (8 mmol, 2 times/week) alone or in combination by gavage for 6 months. β-Carotene supplementation enhanced the pro-inflammatory effects of BaP in the lungs of gerbils. In contrast, quercetin supplementation significantly decreased the infiltration of inflammatory cells as well as the levels of TNF-α and IL-1β in the bronchoalveolar lavage fluid and plasma of gerbils exposed to BaP or BaP+β-carotene (P<.05). Such effects of quercetin supplementation were accompanied by a down-regulation of the expression of phospho-c-Jun and phospho-JNK induced by BaP or BaP+β-carotene in the lungs of gerbils. Furthermore, in the ex vivo study, we found that quercetin-metabolite-enriched plasma (QP) obtained from gerbils acted like a JNK inhibitor to significantly suppress the secretion of pro-inflammatory cytokines induced by BaP or BaP+β-carotene in A549 cells (P<.05). QP also suppressed the activation of the JNK pathway in the A549 cells. These results suggest that supplemental quercetin suppress the pro-inflammatory effect of β-carotene induced by BaP in vivo and ex vivo. The regulation of the JNK pathway by the metabolites of quercetin contributes, at least in part, to such effects of quercetin in vivo.
authors: Department of Nutritional Science, Chung Shan Medical University, Taichung 40201, Taiwan, ROC.
authors: Shu-Ting
authors: ST
authors: Chan
authors: Cheng-Hung
authors: CH
authors: Chuang
authors: Chiao-Lin
authors: CL
authors: Yeh
authors: Jiunn-Wang
authors: JW
authors: Liao
authors: Kai-Li
authors: KL
authors: Liu
authors: Miao-Ju
authors: MJ
authors: Tseng
authors: Shu-Lan
authors: SL
authors: Yeh
mesh_terms: D000818:Animals; D001564:Benzo(a)pyrene / Q000009:adverse effects*; D001992:Bronchoalveolar Lavage Fluid; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism*; D019587:Dietary Supplements; D005786:Gene Expression Regulation / Q000187:drug effects; D005849:Gerbillinae; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D011794:Quercetin / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019207:beta Carotene / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D019207:beta Carotene; D001564:Benzo(a)pyrene; D011794:Quercetin; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4