PMID- 30173052 OWN - NLM STAT- MEDLINE DCOM- 20190222 LR - 20220408 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 64 DP - 2018 Nov TI - 3,4,5-Trihydroxycinnamic acid attenuates lipopolysaccharide (LPS)-induced acute lung injury via downregulating inflammatory molecules and upregulating HO-1/AMPK activation. PG - 123-130 LID - S1567-5769(18)30423-5 [pii] LID - 10.1016/j.intimp.2018.08.015 [doi] AB - The increase in inflammatory cytokines and chemokines is a common denominator in the pathogenesis of acute lung injury (ALI) which are involved in the influx of inflammatory cells and lung damage. The aim of the present study was to evaluate the protective effect of 3,4,5-trihydroxycinnamic acid (THC) in lipopolysaccharide (LPS)-induced ALI. THC efficiently decreased the mRNA expression of interleukin-8 (IL-8) in LPS-stimulated A549 airway epithelial cells. THC induced heme oxygenase-1 (HO-1) expression in A549 cells. THC also increased the activation of AMP-activated protein kinase (AMPK) in A549 cells and RAW264.7 macrophages. In LPS-induced ALI in mice, THC significantly suppressed neutrophil influx and monocyte chemoattractant protein-1 (MCP-1) production in the bronchoalveolar lavage fluid (BALF). THC also attenuated the levels of neutrophil elastase (NE), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in the BALF and serum. In addition, THC inhibited the expressions of inducible nitric oxide synthase (iNOS) and the activation of nuclear factor-kappa B (NF-kappaB) in the lung. These protective effects of THC were accompanied with HO-1 induction and AMPK activation. Taken together, the present study clearly demonstrates that THC significantly attenuates the LPS-induced ALI, suggesting that THC might be a valuable therapeutic adjuvant in airway inflammatory disorders. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Lee, Jae-Won AU - Lee JW AD - Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Chungju-si, Chungbuk 363-883, Republic of Korea. FAU - Chun, Wanjoo AU - Chun W AD - Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon, Kangwon 200-701, Republic of Korea. FAU - Kwon, Ok-Kyoung AU - Kwon OK AD - Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Chungju-si, Chungbuk 363-883, Republic of Korea. FAU - Park, Hyun Ah AU - Park HA AD - Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Chungju-si, Chungbuk 363-883, Republic of Korea. FAU - Lim, Yourim AU - Lim Y AD - Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Chungju-si, Chungbuk 363-883, Republic of Korea. FAU - Lee, Jae-Hyeon AU - Lee JH AD - Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Chungju-si, Chungbuk 363-883, Republic of Korea. FAU - Kim, Doo-Young AU - Kim DY AD - Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Chungju-si, Chungbuk 363-883, Republic of Korea. FAU - Kim, Jung Hee AU - Kim JH AD - Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Chungju-si, Chungbuk 363-883, Republic of Korea. FAU - Lee, Hyeong-Kyu AU - Lee HK AD - Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Chungju-si, Chungbuk 363-883, Republic of Korea. FAU - Ryu, Hyung Won AU - Ryu HW AD - Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Chungju-si, Chungbuk 363-883, Republic of Korea. FAU - Oh, Sei-Ryang AU - Oh SR AD - Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Chungju-si, Chungbuk 363-883, Republic of Korea. Electronic address: seiryang@kribb.re.kr. FAU - Ahn, Kyung-Seop AU - Ahn KS AD - Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Chungju-si, Chungbuk 363-883, Republic of Korea. Electronic address: ksahn@kribb.re.kr. LA - eng PT - Journal Article DEP - 20180831 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Coumaric Acids) RN - 0 (Cytokines) RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) RN - EC 1.14.14.18 (Heme Oxygenase-1) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) RN - EC 3.4.21.37 (Leukocyte Elastase) SB - IM MH - AMP-Activated Protein Kinases/*physiology MH - Acute Lung Injury/chemically induced/*drug therapy MH - Animals MH - Chemokine CCL2/biosynthesis MH - Coumaric Acids/pharmacology/*therapeutic use MH - Cytokines/biosynthesis MH - Heme Oxygenase-1/*physiology MH - Humans MH - Leukocyte Elastase/analysis MH - Lipopolysaccharides/*toxicity MH - Male MH - Mice MH - Mice, Inbred C57BL MH - NF-kappa B/physiology MH - RAW 264.7 Cells OTO - NOTNLM OT - ALI OT - AMPK OT - Airway inflammation OT - HO-1 OT - Neutrophils OT - THC EDAT- 2018/09/03 06:00 MHDA- 2019/02/23 06:00 CRDT- 2018/09/03 06:00 PHST- 2018/03/05 00:00 [received] PHST- 2018/07/04 00:00 [revised] PHST- 2018/08/16 00:00 [accepted] PHST- 2018/09/03 06:00 [pubmed] PHST- 2019/02/23 06:00 [medline] PHST- 2018/09/03 06:00 [entrez] AID - S1567-5769(18)30423-5 [pii] AID - 10.1016/j.intimp.2018.08.015 [doi] PST - ppublish SO - Int Immunopharmacol. 2018 Nov;64:123-130. doi: 10.1016/j.intimp.2018.08.015. Epub 2018 Aug 31.