caa a22 4500 445885262 CHVBK 20180317145557.0 cr unu---uuuuu 170323e20110701xx s 000 0 eng 10.1007/s00011-011-0317-6 doi (NATIONALLICENCE)springer-10.1007/s00011-011-0317-6 Prostaglandin I2 analogues suppress TNF-α expression in human monocytes via mitogen-activated protein kinase pathway [Elektronische Daten] [Wei-Li Wang, Chang-Hung Kuo, Yu-Te Chu, Ching-Hua Huang, Ka-Pan Lam, Shau-Ku Huang, Yuh-Jyh Jong, Yu-Ting Kuo, Chih-Hsing Hung] Objective and design: Although treatment for asthma control has improved a lot recently, refractory asthma is still a challenge for clinicians. Evidence revealed that anti-tumor necrosis factor (TNF)-α therapy may have potential in treating refractory asthma. Recently in an animal model, prostaglandin I2 (PGI2) analogues can suppress the cardinal feature of asthma. However, whether PGI2 analogues can regulate TNF-α expression in monocytes and the mechanism is not well-known. Materials and methods: The human monocytes were pretreated with beraprost, iloprost and treprostinil, three PGI2 analogues, before stimulation with lipopolysaccharide (LPS). TNF-α concentration of the cell supernatants was measured by ELISA. Intracellular signaling was investigated by Western blot. Results: PGI2 analogues suppressed LPS-induced TNF-α expression in THP-1 cells. CAY10449, an I prostanoid receptor antagonist, could reverse these effects. Beraprost increased intracellular cAMP level in THP1 cells. Forskolin, an adenylyl cyclase activator, could confer similar effect. LPS-induced TNF-α expression in THP-1 cells could be reversed by mitogen-activator protein kinase (MAPK)-p38, extracellular signal-related kinase (ERK) and c-Jun N-terminal kinase (JNK) inhibitors. Western blot revealed that beraprost suppressed MAPK phospho-p38, phosphor-JNK and phosphor-ERK expression. Conclusion: PGI2 analogues suppressed LPS-induced TNF-α expression in THP-1 cells via the IP receptor-cAMP and the MAPK pathways. PGI2 analogues may have potentiality to treat asthma. Springer Basel AG, 2011 Tumor necrosis factor α nationallicence I prostanoid receptor nationallicence MAPK pathway nationallicence Monocytes nationallicence Prostaglandin I2 nationallicence Wang Wei-Li Department of Emergency Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan aut Kuo Chang-Hung Department of Pediatrics, Kaohsiung Medical University Hospital, #100, Tz-You 1st Road, 807, Kaohsiung, Taiwan, ROC aut Chu Yu-Te Department of Pediatrics, Kaohsiung Medical University Hospital, #100, Tz-You 1st Road, 807, Kaohsiung, Taiwan, ROC aut Huang Ching-Hua Department of Pediatrics, Yuan's General Hospital, Kaohsiung, Taiwan aut Lam Ka-Pan Department of Pediatrics, Pingtung Christian Hospital, Pingtung, Taiwan aut Huang Shau-Ku Johns Hopkins Asthma and Allergy Center, Johns Hopkins University School of Medicine, 21224, Baltimore, MD, USA aut Jong Yuh-Jyh Department of Pediatrics, Kaohsiung Medical University Hospital, #100, Tz-You 1st Road, 807, Kaohsiung, Taiwan, ROC aut Kuo Yu-Ting Department of Emergency Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan aut Hung Chih-Hsing Department of Pediatrics, Kaohsiung Medical University Hospital, #100, Tz-You 1st Road, 807, Kaohsiung, Taiwan, ROC aut Inflammation Research SP Birkhäuser Verlag Basel 60/7(2011-07-01), 655-663 1023-3830 60:7<655 2011 60 11 https://doi.org/10.1007/s00011-011-0317-6 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00011-011-0317-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Wang Wei-Li Department of Emergency Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan aut NATIONALLICENCE 700 1- Kuo Chang-Hung Department of Pediatrics, Kaohsiung Medical University Hospital, #100, Tz-You 1st Road, 807, Kaohsiung, Taiwan, ROC aut NATIONALLICENCE 700 1- Chu Yu-Te Department of Pediatrics, Kaohsiung Medical University Hospital, #100, Tz-You 1st Road, 807, Kaohsiung, Taiwan, ROC aut NATIONALLICENCE 700 1- Huang Ching-Hua Department of Pediatrics, Yuan's General Hospital, Kaohsiung, Taiwan aut NATIONALLICENCE 700 1- Lam Ka-Pan Department of Pediatrics, Pingtung Christian Hospital, Pingtung, Taiwan aut NATIONALLICENCE 700 1- Huang Shau-Ku Johns Hopkins Asthma and Allergy Center, Johns Hopkins University School of Medicine, 21224, Baltimore, MD, USA aut NATIONALLICENCE 700 1- Jong Yuh-Jyh Department of Pediatrics, Kaohsiung Medical University Hospital, #100, Tz-You 1st Road, 807, Kaohsiung, Taiwan, ROC aut NATIONALLICENCE 700 1- Kuo Yu-Ting Department of Emergency Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan aut NATIONALLICENCE 700 1- Hung Chih-Hsing Department of Pediatrics, Kaohsiung Medical University Hospital, #100, Tz-You 1st Road, 807, Kaohsiung, Taiwan, ROC aut NATIONALLICENCE 773 0- Inflammation Research SP Birkhäuser Verlag Basel 60/7(2011-07-01), 655-663 1023-3830 60:7<655 2011 60 11 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer