3,4,5-Trihydroxycinnamic acid attenuates lipopolysaccharide (LPS)-induced acute lung injury via downregulating inflammatory molecules and upregulating HO-1/AMPK activation

• Published in: International immunopharmacology Vol. 64; pp. 123 - 130
• Main Authors: Lee, Jae-Won, Chun, Wanjoo, Kwon, Ok-Kyoung, Park, Hyun Ah, Lim, Yourim, Lee, Jae-Hyeon, Kim, Doo-Young, Kim, Jung Hee, Lee, Hyeong-Kyu, Ryu, Hyung Won, Oh, Sei-Ryang, Ahn, Kyung-Seop
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2018; Elsevier BV
• Subjects: Acids; Activation; Acute Lung Injury - chemically induced; Acute Lung Injury - drug therapy; Airway inflammation; Airway systems; ALI; Alveoli; AMP; AMP-activated protein kinase; AMP-Activated Protein Kinases - physiology; AMPK; Animals; Attenuation; Bronchus; Chemokine CCL2 - biosynthesis; Chemokines; Coumaric Acids - pharmacology; Coumaric Acids - therapeutic use; Cytokines; Cytokines - biosynthesis; Damage assessment; Elastase; Epithelial cells; Gene expression; Heme; Heme oxygenase (decyclizing); Heme Oxygenase-1 - physiology; HO-1; Humans; Inflammatory diseases; Interleukin 6; Interleukin 8; Leukocyte Elastase - analysis; Lipopolysaccharides; Lipopolysaccharides - toxicity; Lung diseases; Lungs; Macrophages; Male; Mice; Mice, Inbred C57BL; Monocyte chemoattractant protein; Monocyte chemoattractant protein 1; Monocytes; Neutrophils; NF-kappa B - physiology; NF-κB protein; Nitric oxide; Nitric-oxide synthase; Oxygenase; Pathogenesis; Proteins; RAW 264.7 Cells; Respiratory tract; Respiratory tract diseases; THC; Tumor necrosis factor-α; MCP-1; BALF; Neutrophils; HO-1; IL-8; LPS; THC; IL-6; IκB; NF-κB; TNF-α; Airway inflammation; NE; iNOS; AMPK; ALI
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2018.08.015

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-α (TNF-α) 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-κB) 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. •THC reduces the mRNA expression of IL-8 in LPS-stimulated A549 airway epithelial cells.•THC inhibits the influx of neutrophils and macrophages in the BALF of ALI mice.•THC decreases the levels of NE, TNF-α and IL-6 in the BALF and serum.•THC attenuates the recruitment of inflammatory cells and the production of MCP-1 in the lung.•THC downregulates the activation of NF-κB and upregulates the activation of HO-1 and AMPK in the lung.