Stat3 Activation in Acute Lung Injury

Gao, Hongwei; Guo, Renfeng; Speyer, Cecilia L.; Reuben, Jayne S.; Neff, Thomas; Hoesel, Laszlo M.; Riedemann, Niels C.; McClintock, Shannon D.; Sarma, J. Vidya; Rooijen, Nico van; Zetoune, Firas S.; Ward, Peter A.

doi:10.4049/jimmunol.172.12.7703

Cited by 96 publications

(90 citation statements)

References 50 publications

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“…Tissue-specific Stat3 gene deletion mouse models have also defined an important role of Stat3 in tissue injury and wound healing in epithelial cells of the lung and skin (Sano et al, 1999;Gao et al, 2004;Hokuto et al, 2004;Severgnini et al, 2004). In lung epithelial cells, Stat3 is activated in acute lung injury and loss of Stat3 compromises survival following hyperoxia (Gao et al, 2004;Hokuto et al, 2004;Severgnini et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…In addition to processes involved in tumor formation in epithelial cells, Stat3 plays a crucial role in normal wound healing and response to injury. Stat3 is activated in lung tissues following either lipopolysaccharide (LPS) exposure or intrapulmonary deposition of IgG immune complexes (Gao et al, 2004;Severgnini et al, 2004). Selective Stat3 deletion in lung epithelial cells does not compromise postnatal lung function but mice exposed to hyperoxia develop rapid lung injury characterized by alveolar capillary leak and acute respiratory distress (Hokuto et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Stat3 regulates genes common to both wound healing and cancer

et al. 2005

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Stat3 regulates genes common to both wound healing and cancer

et al. 2005

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“…Activated Jaks phosphorylate the cytoplasmic domain of the receptor, creating a docking site for Src homology 2-containing proteins such as STAT transcription factors (14). Indeed, our previous work showed that STAT3 is activated in lung during IgG IC-induced acute lung injury, with both Tyr 705 and Ser 727 undergoing phosphorylation (15). Activation of STAT3 in lungs is macrophage and neutrophil dependent.…”

Section: Adenoviral-mediated Overexpression Of Socs3 Enhances Iggmentioning

confidence: 99%

Adenoviral-Mediated Overexpression of SOCS3 Enhances IgG Immune Complex-Induced Acute Lung Injury

Gao

Hoesel

Guo

et al. 2006

The Journal of Immunology

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The lung inflammatory response caused by intratracheal deposition of IgG immune complexes (IC) includes the production of IL-6, which signals through activation of STAT transcription factors. Recently, suppressor of cytokine signaling 3 (SOCS3) has been shown to be a key negative regulator of IL-6/gp130/Jak/STAT3 signal transduction. Although SOCS3 has been implicated in several inflammatory diseases, very little is known regarding its activation and its function in the lung during acute inflammation. Our previous study showed that IL-6/STAT3 activation was triggered in lungs after intrapulmonary deposition of IgG IC in rats. In the current study, we sought to determine whether SOCS3 is playing a regulatory role in the lung inflammatory response. SOCS3 induction occurred during development of inflammation in the IgG IC model of lung injury. Overexpression of SOCS3 in lung using a recombinant adenovirus encoding murine SOCS3 resulted in substantial increases in lung vascular permeability and lung myeloperoxidase, together with enhanced levels of TNF-α, MIP-2, and keratinocyte-activated cytokine in bronchoalveolar lavage fluids. SOCS3 overexpression in lungs led to overproduction of bronchoalveolar lavage IL-6, but not IL-10, in this inflammatory model. We further show that activation of STAT3 was inhibited by SOCS3 overexpression as well as by anti-IL-6 treatment during IgG IC-induced lung injury, as determined by EMSA. In vitro, SOCS3 overexpression abrogated IL-6-induced activation of STAT3 in lung epithelial cells. These findings suggest SOCS3 is an important regulator of lung inflammatory injury after deposition of IgG IC.

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“…Recently, phosphorylation of STAT-1 on serine residue 727 was implicated in STAT-1-mediated effects (41,42). To determine whether serine 727 phosphorylation was induced by IL-10 in monocytic cells, we treated purified monocytes and HL-60 cells with IL-10 for 0 -60 min.…”

Section: Il-10-induced Cd14 Expression Involves the Activation Of Stat-1mentioning

confidence: 99%

STAT-1 Mediates the Stimulatory Effect of IL-10 on CD14 Expression in Human Monocytic Cells

Rahimi

Gee

Mishra

et al. 2005

The Journal of Immunology

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IL-10, an anti-inflammatory cytokine, has been shown to exhibit stimulatory functions including CD14 up-regulation on human monocytic cells. CD14-mediated signaling following LPS stimulation of monocytic cells results in the synthesis of proinflammatory cytokines. Our results show that LPS-induced CD14 expression on monocytic cells may be mediated by endogenously produced IL-10. To investigate the molecular mechanism by which IL-10 enhances CD14 expression, both human monocytes and the promyelocytic HL-60 cells were used as model systems. IL-10 induced the phosphorylation of PI3K and p42/44 ERK MAPK. By using specific inhibitors for PI3K (LY294002) and ERK MAPKs (PD98059), we demonstrate that LY294002 either alone or in conjunction with PD98059 inhibited IL-10-induced phosphorylation of STAT-1 and consequently CD14 expression. However, IL-10-induced STAT-3 phosphorylation remained unaffected under these conditions. Finally, STAT-1 interfering RNA inhibited IL-10-induced CD14 expression. Taken together, these results suggest that IL-10-induced CD14 up-regulation in human monocytic cells may be mediated by STAT-1 activation through the activation of PI3K either alone or in concert with the ERK MAPK.

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Stat3 Activation in Acute Lung Injury

Cited by 96 publications

References 50 publications

Stat3 regulates genes common to both wound healing and cancer

Stat3 regulates genes common to both wound healing and cancer

Adenoviral-Mediated Overexpression of SOCS3 Enhances IgG Immune Complex-Induced Acute Lung Injury

STAT-1 Mediates the Stimulatory Effect of IL-10 on CD14 Expression in Human Monocytic Cells

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