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ARS Home » Plains Area » Grand Forks, North Dakota » Grand Forks Human Nutrition Research Center » Dietary Prevention of Obesity-related Disease Research » Research » Publications at this Location » Publication #276457
Title: An essential role for the Stat3 in regulating IgG immune complex-induced pulmonary inflammation

Author
item TANG, HUIFANG - Harvard Institute Of Medicine
item YAN, CHUNGYANG - Harvard Institute Of Medicine
item Cao, Jay
item SARMA, J - University Of Michigan
item HAURA, ERIC - University Of South Florida
item WU, MIN - University Of North Dakota
item GAO, HONGWEI - Harvard Institute Of Medicine

Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/11/2011
Publication Date: 12/7/2011
Citation: Tang, H., Yan, C., Cao, J.J., Sarma, J.V., Haura, E.B., Wu, M., Gao, H. 2011. An essential role for the Stat3 in regulating IgG immune complex-induced pulmonary inflammation. Journal of Federation of American Societies for Experimental Biology. 25:4292-4300.

Interpretive Summary: Signal transducer and activator of transcription (Stat) 3 plays an important role during inflammation. However, the function of Stat3 in acute lung injury (ALI) in not fully understood. Using an adenoviral vector expressing a dominant-negative Stat3 isoform, we determined the role of Stat3 in IgG immune complexes (IC)-induced inflammatory reponses 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. We demonstrate that both lung vascular permeability (albumin leak) and lung myeloperoxidase accumulation were substantially by Stat3. Furthermore, we found that Stat3 caused significant decrease in neutrophils, some inflammatory cytokines, chemokines, and complement component C5a in bronchoalveolar lavage fluids. Our results suggest that Stat3 mediates the acute inflammatory response and alveolar macrophages of animal with IgG immune complexes-induced lung injury.

Technical 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 ICinduced 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- and IL-6), chemokines [keratinocyte cell-derived chemokine, macrophage inflammatory protein (MIP)-1, and MIP-1], 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.—Tang, H., Yan, C., Cao, J., Sarma, J. V., Haura, E. B., Wu, M., Gao, H. An essential role for Stat3 in regulating IgG immune complex-induced pulmonary inflammation.