Paralemmin-3 contributes to lipopolysaccharide-induced inflammatory response and is involved in lipopolysaccharide-Toll-like receptor-4 signaling in alveolar macrophages

Chen,Xu-Xin; Tang,Lu; Fu,Yu-Mei; Wang,Yi; Han,Zhi-Hai; Meng,Ji-Guang

doi:10.3892/ijmm.2017.3161

Paralemmin-3 contributes to lipopolysaccharide-induced inflammatory response and is involved in lipopolysaccharide-Toll-like receptor-4 signaling in alveolar macrophages

Authors:
- Xu-Xin Chen
- Lu Tang
- Yu-Mei Fu
- Yi Wang
- Zhi-Hai Han
- Ji-Guang Meng
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Affiliations: Department of Respiratory Medicine, Navy General Hospital of the PLA, Beijing 100037, P.R. China, Department of Neurology, The First Hospital of Changsha, Changsha, Hunan 430100, P.R. China, Department of Emergency, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China, Department of Respiratory Medicine, The Sixth People's Hospital of Jinan City Affiliated to Jining Medical College, Jinan, Shandong 250200, P.R. China
Published online on: September 28, 2017 https://doi.org/10.3892/ijmm.2017.3161
Pages: 1921-1931

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Abstract

Alveolar macrophages (AMs) are the first line of defense against foreign stimulation in alveoli, and they participate in inflammatory responses during acute lung injury (ALI). Previous studies indicated that paralemmin-3 (PALM3) expression is induced by lipopolysaccharides (LPS) and may be involved in LPS-Toll-like receptor 4 (TLR4) signaling in alveolar epithelial cells. The aim of the present study was to investigate the effect of PALM3 on LPS-induced inflammation and its underlying mechanisms in rat AMs. For this purpose, the authors detected the expression of PALM3 in AMs by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting following LPS stimulation. Following this, a recombinant adenovirus expressing short hairpin RNA (shRNA) for PALM3 was constructed, as well as a recombinant adenovirus carrying the rat PALM3 gene to modulate the expression of PALM3 in rat AMs. At 48 h after transfection, the PALM3 expression in AMs was detected by RT-qPCR and western blotting. The levels of several cytokines and the activity of nuclear factor-κB and interferon regulatory factor 3 in AMs were measured after LPS stimulation. The localization of PALM3 and LPS-TLR4 signaling adaptor molecules in AMs was analyzed by confocal microscopy, and the physical interactions of PALM3 with these adaptors were assessed by co-immunoprecipitation assays. LPS induced PALM3 expression in AMs and that PALM3 expression promoted the LPS-induced inflammatory response, while PALM3 downregulation suppressed the LPS-induced inflammatory response in AMs. In addition, the results demonstrated that PALM3 could interact with TLR4, myeloid differentiation factor 88, interleukin (IL)-1 receptor associated kinase-1, tumor necrosis factor receptor associated factor-6, and Toll-IL-1 receptor containing adapter molecule-2 in AMs after LPS stimulation. These results suggested that PALM3 contributes to the LPS-induced inflammatory response and participates in LPS-TLR4 signaling in AMs. These data may provide the basis for the development of novel targeted therapeutic strategies of treating ALI.

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