title: In vitro inflammatory effects of polyhexamethylene biguanide through NF-κB activation in A549 cells.
abstract: Polyhexamethylene biguanide (PHMB) is a member of the polymeric guanidine family, which is used as a biocide and preservative in industrial, medicinal, and consumer products. Some studies reported that polyhexamethylene guanidine phosphate, which is also a member of the guanidine family, induced severe inflammation and fibrosis in the lungs. However, limited studies have evaluated the pulmonary toxicity of PHMB associated with inflammatory responses. The aim of this study was to elucidate the inflammatory responses and its mechanisms induced by PHMB in lung cells. A549 cells exposed to PHMB showed decreased viability, reactive oxygen species (ROS) generation, inflammatory cytokine secretion, and nuclear factor kappa B (NF-κB) activation. The cells showed dose-dependent cytotoxicity and slight generation of ROS. PHMB triggered inflammatory cytokine secretion and NF-κB activation by modulating the degradation of IκB-α and the accumulation of nuclear p65. TNF-α plays important roles in IL-8 expression as well as NF-κB activation. Moreover, IL-8 production induced by PHMB was completely suppressed by a NF-κB inhibitor, but not by a ROS scavenger. In conclusion, we suggest that PHMB induces the inflammatory responses via the NF-κB signaling pathway.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon-si, Gyeonggi-do 16419, South Korea; Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-ku, Sendai 980-8578, Japan.
authors.forename: Ha Ryong
authors.initials: HR
authors.lastname: Kim
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon-si, Gyeonggi-do 16419, South Korea.
authors.forename: Da Young
authors.initials: DY
authors.lastname: Shin
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon-si, Gyeonggi-do 16419, South Korea. Electronic address: khchung@skku.edu.
authors.forename: Kyu Hyuck
authors.initials: KH
authors.lastname: Chung
mesh_terms: D000072283:A549 Cells; D001645:Biguanides / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D004202:Disinfectants / Q000633:toxicity*; D007249:Inflammation / Q000139:chemically induced* / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001645:Biguanides; D004202:Disinfectants; C508600:IL6 protein, human; D015850:Interleukin-6; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C031233:polihexanide
keywords: Inflammation; Nuclear factor kappa B; Polyhexamethylene biguanide; Reactive oxygen species; Tumor necrosis factor alpha