PMID- 30078834 OWN - NLM STAT- MEDLINE DCOM- 20180816 LR - 20180816 IS - 1880-3989 (Electronic) IS - 0388-1350 (Linking) VI - 43 IP - 8 DP - 2018 TI - Polyhexamethylene guanidine phosphate induces IL-6 and TNF-alpha expression through JNK-dependent pathway in human lung epithelial cells. PG - 485-492 LID - 10.2131/jts.43.485 [doi] AB - 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-alpha, 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-alpha 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-alpha. These results suggest that the activation of JNK is involved at least partially in the induction of IL-6 or TNF-alpha expression by PHMG in A549 cells. FAU - Kim, Min-Seok AU - Kim MS AD - National Center for Efficacy Evaluation of Respiratory Disease Product, Korea Institute of Toxicology, Korea. FAU - Han, Jin-Young AU - Han JY AD - National Center for Efficacy Evaluation of Respiratory Disease Product, Korea Institute of Toxicology, Korea. AD - Department of human and environmental toxicology, University of Science & Technology, Korea. FAU - Kim, Sung-Hwan AU - Kim SH AD - National Center for Efficacy Evaluation of Respiratory Disease Product, Korea Institute of Toxicology, Korea. AD - Department of human and environmental toxicology, University of Science & Technology, Korea. FAU - Kim, Hyung-Young AU - Kim HY AD - National Center for Efficacy Evaluation of Respiratory Disease Product, Korea Institute of Toxicology, Korea. FAU - Jeon, Doin AU - Jeon D AD - National Center for Efficacy Evaluation of Respiratory Disease Product, Korea Institute of Toxicology, Korea. FAU - Lee, Kyuhong AU - Lee K AD - National Center for Efficacy Evaluation of Respiratory Disease Product, Korea Institute of Toxicology, Korea. AD - Department of human and environmental toxicology, University of Science & Technology, Korea. LA - eng PT - Journal Article PL - Japan TA - J Toxicol Sci JT - The Journal of toxicological sciences JID - 7805798 RN - 0 (Anti-Infective Agents) RN - 0 (Guanidines) RN - 0 (Interleukin-6) RN - 0 (RNA, Messenger) RN - 0 (Tumor Necrosis Factor-alpha) RN - 31961-54-3 (polyhexamethyleneguanidine) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) SB - IM MH - A549 Cells MH - Animals MH - Anti-Infective Agents/*adverse effects MH - Epithelial Cells/*metabolism MH - Extracellular Signal-Regulated MAP Kinases/metabolism MH - Gene Expression/drug effects MH - Guanidines/*adverse effects MH - Humans MH - Interleukin-6/genetics/*metabolism MH - JNK Mitogen-Activated Protein Kinases/metabolism MH - Lung/*metabolism MH - MAP Kinase Signaling System/*drug effects MH - Mice, Inbred C57BL MH - RNA, Messenger/genetics/metabolism MH - Tumor Necrosis Factor-alpha/genetics/*metabolism MH - p38 Mitogen-Activated Protein Kinases/metabolism OTO - NOTNLM OT - Cytokine OT - Inflammation OT - MAPKs OT - PHMG OT - Pulmonary fibrosis EDAT- 2018/08/07 06:00 MHDA- 2018/08/17 06:00 CRDT- 2018/08/07 06:00 PHST- 2018/08/07 06:00 [entrez] PHST- 2018/08/07 06:00 [pubmed] PHST- 2018/08/17 06:00 [medline] AID - 10.2131/jts.43.485 [doi] PST - ppublish SO - J Toxicol Sci. 2018;43(8):485-492. doi: 10.2131/jts.43.485.