title: Myeloid differentiation protein 2 silencing decreases LPS-induced cytokine production and TLR4/MyD88 pathway activity in alveolar macrophages.
abstract: Lipopolysaccharides (LPSs) activate the innate immune response during Gram-negative bacterial infections through the Toll-like receptor 4 (TLR4)/myeloid differentiation protein 2 (MD-2) complex. MD-2 binds LPS with high affinity and is critical for TLR4-dependent signal transduction. However, the exact role of MD-2 on LPS signal transduction and cytokine production in alveolar macrophages (AMs) remains unclear. This study showed that the transcription levels of MD-2, TLR4 and MyD88 in the NR8383 cell line were up-regulated after LPS stimulation and that the increased transcript levels were attenuated after RNA interference of MD-2. Similarly, LPS induced increases in TNF-α, IL-1β and IL-6 protein levels in NR8383 cell supernatants was significantly inhibited by MD-2 silencing. These results suggest that in association with the TLR4/MyD88 signaling pathway LPS-induced cytokine production can be partially reduced by MD-2 silencing in the rat pulmonary alveolar macrophage cell line NR8383. MD-2 silencing was proved to be a useful tool for testing the role of MD-2 in the LPS signaling pathway and may be a potential therapeutic tool against LPS-induced lung inflammation.
authors.affiliation: Department of Geriatric, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Weiying
authors.initials: W
authors.lastname: Ren
authors.forename: Lijuan
authors.initials: L
authors.lastname: Hu
authors.forename: Feng
authors.initials: F
authors.lastname: Hua
authors.forename: Jianjun
authors.initials: J
authors.lastname: Jin
authors.forename: Yanying
authors.initials: Y
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Zhu
mesh_terms: D000818:Animals; D002460:Cell Line; D053583:Interleukin-1beta / Q000032:analysis / Q000037:antagonists & inhibitors; D015850:Interleukin-6 / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051218:Lymphocyte Antigen 96 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D011014:Pneumonia / Q000628:therapy; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000037:antagonists & inhibitors; D000093242:Interleukin-6 Inhibitors
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D051218:Lymphocyte Antigen 96; D053594:Myeloid Differentiation Factor 88; D034741:RNA, Small Interfering; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C507781:Myd88 protein, rat; C495347:Tlr4 protein, rat