期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 112, 期 4, 页码 598-607出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI200317129
关键词
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Regulated recruitment and clearance of neutrophils (PMN) is the hallmark of competent host defense and resolution of inflammation. We now report that IFN-gamma controls PMN infiltration and modulates IL-6 signaling through its soluble receptor (sIL-6R) to promote their apoptosis and clearance. Induction of peritoneal inflammation in IFN-gamma-deficient (IFN-gamma(-/-)) mice emphasized that the initial rate of PMN recruitment was impaired. This defect in PMN recruitment was also associated with the suppressed intraperitoneal expression of IL-1beta and IL-6. Reconstitution of IFN-gamma signaling restored the rate of PMN infiltration and IL-6 levels and was accompanied by normalization of PMN-activating CXC chemokine expression. To test whether local IL-6 signaling modulated PMN recruitment, inflammation was induced in IFN-gamma(-/-) and IL-6(-/-) mice and cytokine signaling adapted by intraperitoneal sIL-6R-IL-6 fusion protein (HYPER-IL-6) or IFN-gamma. Although HYPER-IL-6 attenuated PMN influx in IFN-gamma(-/-) mice, IFN-gamma had no effect on PMN infiltration in IL-6-1 mice. Examination of the leukocyte infiltrate from IFN-gamma(-/-), IL-6(-/-), and wild-type mice showed that apoptosis was aberrant in the absence of IFN-gamma(-/-) and IL-6(-/-) as a result of impaired sIL-6R signaling. These data emphasize a pivotal role for IFN-gamma in regulating innate immunity through control of both the recruitment and clearance phases of PMN trafficking.
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