Polyhexamethylene guanidine phosphate induces IL-6 and TNF-α expression through JNK-dependent pathway in human lung epithelial cells

• Published in: Journal of toxicological sciences Vol. 43; no. 8; pp. 485 - 492
• Main Authors: Kim, Min-Seok, Lee, Kyuhong, Kim, Sung-Hwan, Kim, Hyung-Young, Han, Jin-Young, Jeon, Doin
• Format: Journal Article
• Language: English
• Published: Japan The Japanese Society of Toxicology 01.01.2018; Japan Science and Technology Agency
• Subjects: A549 Cells; Animals; Anti-Infective Agents - adverse effects; Biocides; Cytokine; Cytokines; Epithelial cells; Epithelial Cells - metabolism; Extracellular Signal-Regulated MAP Kinases - metabolism; Fibrosis; Gene expression; Gene Expression - drug effects; Guanidine; Guanidines - adverse effects; Humans; In vivo methods and tests; Inflammation; Inflammatory response; Inhibitors; Interleukin 6; Interleukin-6 - genetics; Interleukin-6 - metabolism; JNK Mitogen-Activated Protein Kinases - metabolism; Lung - metabolism; Lungs; MAP kinase; MAP Kinase Signaling System - drug effects; MAPKs; Mice, Inbred C57BL; p38 Mitogen-Activated Protein Kinases - metabolism; PHMG; Phosphorylation; Pretreatment; Pulmonary fibrosis; RNA, Messenger - genetics; RNA, Messenger - metabolism; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α; Inflammation; Pulmonary fibrosis; Cytokine; PHMG; MAPKs
• ISSN: 0388-1350; 1880-3989; 1880-3989
• DOI: 10.2131/jts.43.485

Polyhexamethylene guanidine phosphate (PHMG) is an antimicrobial biocide that causes severe lung injury accompanied with inflammation and subsequent fibrosis. Cytokines mediate the inflammatory response, leading to fibrosis in injured tissues. PHMG is known to induce the expression of various cytokines in vitro and in vivo. In the present study, we investigated the involvement of three MAPK subfamilies (JNK, p38 MAPK, and ERK) in PHMG-induced cytokine expression in A549 human lung epithelial cells. Our in vivo and in vitro data indicated that PHMG induced an increase in mRNA expression of IL-6 and TNF-α, and enhanced the phosphorylation of JNK, p38 MAPK, and ERK. Further, we investigated the involvement of MAPKs in PHMG-induced mRNA expression of IL-6 and TNF-α using JNK, p38 MAPK, and ERK inhibitors in A549 cells. Pre-treatment with the JNK inhibitor but not the p38 MAPK or ERK inhibitor, significantly attenuated the PHMG-induced mRNA expression of IL-6 and TNF-α. These results suggest that the activation of JNK is involved at least partially in the induction of IL-6 or TNF-α expression by PHMG in A549 cells.