CXCR3 May Help Regulate the Inflammatory Response

Authors: Li Nie Wei Wu Zhibing Lu Gangyan Zhu Juan Liu

Publish Date: 2015/10/16

Volume: 39, Issue: 2, Pages: 526-533

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Abstract

The aim of this study is to investigate the role of CXCR3 and IL10 in lipopolysaccharide LPSinduced acute lung injury ALI ALI was induced by LPS injection 10 mg/kg via the tail vein in C57BL/6 mice Mice were sacrificed after 2 or 12 h to examine the levels of inflammatory cytokines in bronchoalveolar lavage fluid BALF and histopathologic assessments At 12 h after LPS injection mice exhibited more severe lung infiltration by CD8+ T cell and less infiltration by CD8+CD122+ regulatory T cells than at 2 h after LPS challenge or in the control mice not exposed to LPS At 12 h IFNγ CXCR3 and CXCL10 were significantly higher in the lungs IL10 in the lungs was significantly lower CXCR3 may help to recruit CD8+ T cells and promotes IFNγ and CXCL10 release Such effects could be inhibited by IL10 secreted by CD8+CD122+ regulatory T cellsAcute lung injury ALI and acute respiratory distress syndrome ARDS are frequent complications in patients with burns trauma and sepsis and they are associated with high rates of morbidity and mortality 1 Infection or mechanical injury triggers a generalized inflammatory response involving various inflammatory cells and proinflammatory mediators In particular several studies suggest that the chemokine receptor CXCR3 which is expressed primarily on activated T lymphocytes natural killer NK cells and some epithelial cells can trigger an inflammatory response cascade at sites of ALI by recruiting CD8+ T cells and promoting release of proinflammatory interferonγ IFNγ and chemokine CXCL10 2The body is capable of mitigating the inflammation in ALI by releasing antiinflammatory mediators at injury sites leading investigators to examine how the disbalance between pro and antiinflammatory factors may drive ALI and may be manipulated for therapeutic effects 3 4 5 For example interleukin10 IL10 secreted by CD8+CD122+ regulatory T cells has been shown to inhibit CD8+ T cells and reduce inflammation in various inflammatory diseases 6 However whether CD8+CD122+ regulatory T cells and IL10 regulate CXCR3 activity in ALI has not been reportedHealthy male C57BL/6 mice aged 10–12 weeks and weighing 20–22 g SJA Laboratory Animals Hunan Chinawere randomly divided into a control group n = 8 and two ALI groups n = 8 each At baseline control mice were injected in the tail vein with 1 ml saline while ALI mice were injected with 10 mg/kg lipopolysaccharide Sigma Beijing China dissolved in 1 ml saline One group of ALI mice was sacrificed by pentobarbital overdose at 2 h after injection while the other ALI group as well as the control group was sacrificed at 12 h after injectionThe lower lobe of the left lung was removed inflated to 250 mmH2O with 10  formal in fixed overnight embedded in paraffin and sectioned to a thickness of 5 μm Sagittal sections were stained with hematoxylineosin HE for histopathologic assessments under a light microscope Olympus Japan by an experience pathologist blinded to treatment conditionsTracheas of sacrificed animals were intubated with a 20gauge catheter Bronchoalveolar lavage fluid BALF was collected by flushing twice with 08 mL of icecold phosphatebuffered saline PBS A total injected volume of 15 mL was recovered in 95  of mice The recovered BALF was centrifuged at 1500 rpm for 5 min at 4 °C and the supernatant was stored at −70 °C for subsequent assay of cytokines and chemokines Total cells were counted on a hemocytometer For differential cell counting cells were spun onto glass slides fixed and stained with DiffQuik reagents Beijing Chemical Works Beijing China Numbers of macrophages neutrophils and lymphocytes per 400 cells were determined based on morphology

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