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FASEB J. 2011 Dec;25(12):4292-300. doi: 10.1096/fj.11-187955. Epub 2011 Aug 22.

An essential role for Stat3 in regulating IgG immune complex-induced pulmonary inflammation.

Author information

1
Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women's Hospital, Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Medical School, Boston, MA 02115, USA.

Abstract

Growing evidence suggests that transcription factor signal transducer and activator of transcription (Stat) 3 may play an important regulatory role during inflammation. However, the function of Stat3 in acute lung injury (ALI) is largely unknown. In the current study, by using an adenoviral vector expressing a dominant-negative Stat3 isoform (Ad-Stat3-EVA), we determined the role of Stat3 in IgG immune complex (IC)-induced inflammatory responses and injury in the lung from C57BL/6J mice. We show that IgG IC-induced DNA binding activity of Stat3 in the lung was significantly inhibited by Stat3-EVA. We demonstrate that both lung vascular permeability (albumin leak) and lung myeloperoxidase accumulation in the Ad-Stat-EVA treated mice were substantially reduced when compared with values in mice receiving control virus (Ad-GFP) during the injury. Furthermore, intratracheal administration of Ad-Stat3-EVA caused significant decreases in the contents of neutrophils, inflammatory cytokines (TNF-α and IL-6), chemokines [keratinocyte cell-derived chemokine, macrophage inflammatory protein (MIP)-1α, and MIP-1β], and complement component C5a in bronchoalveolar lavage fluids. Using Stat3-specific small interfering RNA, we show that knocking down Stat3 expression in alveolar macrophages (MH-S cells) significantly reduced the production of proinflammatory mediators on IgG IC stimulation. These data suggest that Stat3 plays an essential role in the pathogenesis of IgG IC-induced ALI by mediating the acute inflammatory responses in the lung and alveolar macrophages.

PMID:
21859893
PMCID:
PMC3236634
DOI:
10.1096/fj.11-187955
[Indexed for MEDLINE]
Free PMC Article

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