Pollutant particles induce arginase II in human bronchial epithelial cells.
Exposure to particulate matter (PM) is associated with adverse pulmonary effects, including induction and exacerbation of asthma. Recently arginase was shown to play an important role in the pathogenesis of asthma. In this study, it was postulated that PM exposure might induce arginase. Human bronchial epithelial cells (HBEC) obtained from normal individuals by endobronchial brushings cultured on an air-liquid interface were incubated with fine Chapel Hill particles (PM₂.₅, 100 μg/ml) for up to 72 h. Arginase activity, protein expression, and mRNA of arginase I and arginase II were measured. PM₂.₅ increased arginase activity in a time-dependent manner. The rise was primarily due to upregulation of arginase II. PD153035 (10 μM), an epidermal growth factor (EGF) receptor antagonist, attenuated the PM₂.₅-induced elevation in arginase activity and arginase II expression. Treatment of HBEC with human EGF increased arginase activity and arginase II expression. Pretreatment with catalase (200 U/ml), superoxide dismutase (100 U/ml), or apocynin (5 μg/ml), an NAD(P)H oxidase inhibitor, did not markedly affect arginase II expression. Treatment of HBEC with arginase II siRNA inhibited the expression of arginase II by 60% and increased IL-8 release induced by PM₂.₅. These results indicate that PM exposure upregulates arginase II activity and expression in human bronchial epithelial cells, in part via EGF-dependent mechanisms independent of oxidative stress. The elevated arginase II activity and expression may be a mechanism underlying adverse effects induced by PM exposure in asthma patients.
National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA.
Xhevahire
X
Hyseni
Joleen M
JM
Soukup
Yuh-Chin T
YC
Huang
D000393:Air Pollutants / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D001119:Arginase / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D001249:Asthma / Q000139:chemically induced / Q000201:enzymology; D001980:Bronchi / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D004790:Enzyme Induction / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D009657:North Carolina; D052638:Particulate Matter / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D011994:Recombinant Proteins / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
D000393:Air Pollutants; C508606:CXCL8 protein, human; D016209:Interleukin-8; D007527:Isoenzymes; D052638:Particulate Matter; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; C574619:ARG1 protein, human; C477631:ARG2 protein, human; D001119:Arginase