Pro-inflammatory and Pro-apoptotic Role of IL-33 in the Human Acute Lung Injury (ALI) Development

Author(s): Guoquan Pan, Yafeng Liang, Xu Chen, Lu Lu, Linxia Wang, Min Wang, Xiaojiao Ye, Chunxue Yan.

Journal Name: Current Signal Transduction Therapy

Volume 10 , Issue 1 , 2015

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Abstract:

The development of acute lung injury (ALI) is always accompanied by remarkably increased production of cytokines in plasma. However, the pathogenesis of this inflammatory response is unclear. In this study, the hypothesis whether Interleukin 33 (IL-33) is induced in the ALI patients and the possible mechanism was tested. The levels of IL-33 were found to be significantly induced in plasma of the ALI patients. Addition of IL-33, enhanced mRNA expression of NLRP-3, Caspase-3, BAX and p53 of peripheral mononuclear blood cells (PBMCs), but inhibited mRNA expression of Caspase-1 found in ALI patients. By stimulating the PBMCs with recombinant Human Interleukin (rhIL)-33, we demonstrated that the chemokines Interleukin 1β (IL-1β), Interleukin 6 (IL-6), Interleukin 18 (IL-18) and Tumor Necrosis Factor (TNF-α) were significantly increased with IL-33 administration in a dose dependent way. Concomitantly, the increase of phosphorylated p38 and enhancement of cell apoptosis were also found in the PBMCs. However, by blocking the IL-33 signaling with p38 inhibitor (SB 203580), the cytokine production and apoptosis were apparently blocked in PBMCs. The present study provided evidences for the IL-33 molecular mechanism in ALI patients. It promots cell apoptosis and cytokines production via the MAPK/p38 signaling in PBMCs.

Keywords: Acute lung injury (ALI), inflammation, IL-33, PBMCs, p38.

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Article Details

VOLUME: 10
ISSUE: 1
Year: 2015
Page: [48 - 55]
Pages: 8
DOI: 10.2174/1574362410666150407232651

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