title: An essential role for Stat3 in regulating IgG immune complex-induced pulmonary inflammation.
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.
authors.affiliation: 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.
authors.forename: Huifang
authors.initials: H
authors.lastname: Tang
authors.forename: Chunguang
authors.initials: C
authors.lastname: Yan
authors.forename: Jay
authors.initials: J
authors.lastname: Cao
authors.forename: J Vidya
authors.initials: JV
authors.lastname: Sarma
authors.forename: Eric B
authors.initials: EB
authors.lastname: Haura
authors.forename: Min
authors.initials: M
authors.lastname: Wu
authors.forename: Hongwei
authors.initials: H
authors.lastname: Gao
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D001483:Base Sequence; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D055785:Gene Knockdown Techniques; D007074:Immunoglobulin G / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009195:Peroxidase / Q000378:metabolism; D011014:Pneumonia / Q000276:immunology* / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000936:Antigen-Antibody Complex; D018925:Chemokines; D016207:Cytokines; D007074:Immunoglobulin G; D018836:Inflammation Mediators; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D004247:DNA; D009195:Peroxidase