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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





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Title:   Author  item
                                            TANG, HUIFANG - Harvard Institute Of Medicineitem
                                            YAN, CHUNGYANG - Harvard Institute Of Medicineitem
                                            Cao, Jayitem
                                            SARMA, J - University Of Michiganitem
                                            HAURA, ERIC - University Of South Floridaitem
                                            WU, MIN - University Of North Dakotaitem
                                            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.


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