title: Blockage of thymic stromal lymphopoietin signaling improves acute lung injury in mice by regulating pulmonary dendritic cells.
abstract: OBJECTIVE
  To investigate the effects of blockage of thymic stromal lymphopoietin (TSLP) signaling by TSLP receptor (TSLPR)-immunoglobulin (Ig) on acute lung injury (ALI) induced by lipopolysaccharide (LPS).
  
  
  METHODS
  C57BL/6 mice received TSLPR-Ig or controlled-Ig before being induced ALI. Lung wet/dry (W/D) weight ratio was recorded. Neutrophil number and albumin concentration of bronchoalveolar lavages fluids (BALF) were determined. Besides, bone marrow dendritic cells (BMDCs) were separated and cultured with medium, TSLP, TSLP plus TSLPR-Ig or TSLP plus controlled-Ig. Protein expression levels of TSLP in lung tissues, phosphorylation extracellular regulated protein kinases (pERK) 1/2, p38, and signal transducers and activators of transcription (STAT) 3 in BMDCs were analyzed using Western blotting. Expression of CD40, CD80 and CD86 on pulmonary DCs and BMDCs was determined using flow cytometry (FCM).
  
  
  RESULTS
  The W/D ratio, neutrophil number and albumin concentration were significantly decreased in the TSLPR-Ig group compared with the controlled-Ig and model group. Moreover, there was a noticeable decrease in CD40, CD80 or CD86 expression by TSLPR-Ig on both pulmonary DCs and BMDCs. The protein levels of TSLP, pERK1 and STAT3 were significantly decreased by TSLPR-Ig. However, no significant differences were found in p38 and pERK2.
  
  
  CONCLUSIONS
  These results suggest that TSLP may be involved in ALI, and blockage of TSLP signaling using TSLPR-Ig improves ALI at least in part by regulation of DCs functions. The underling downstream signaling mediated by TSLP might be associated with activating the ERK1 and STAT3 signaling pathway.
authors.affiliation: Department of Pediatric Intensive Care Unit, The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University Wenzhou 325000, Zhejiang, China.
authors.forename: Guoquan
authors.initials: G
authors.lastname: Pan
authors.affiliation: Department of Pediatric Intensive Care Unit, The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University Wenzhou 325000, Zhejiang, China.
authors.forename: Yafeng
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Pediatric Intensive Care Unit, The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University Wenzhou 325000, Zhejiang, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Pediatric Intensive Care Unit, The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University Wenzhou 325000, Zhejiang, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Pediatric Intensive Care Unit, The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University Wenzhou 325000, Zhejiang, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Pediatric Intensive Care Unit, The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University Wenzhou 325000, Zhejiang, China.
authors.forename: Linxia
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pediatric Intensive Care Unit, The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University Wenzhou 325000, Zhejiang, China.
authors.forename: Chunxue
authors.initials: C
authors.lastname: Yan
authors.affiliation: Department of Pediatric Intensive Care Unit, The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University Wenzhou 325000, Zhejiang, China.
authors.forename: Weixi
authors.initials: W
authors.lastname: Zhang
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D018122:B7-1 Antigen / Q000276:immunology / Q000378:metabolism; D051940:B7-2 Antigen / Q000276:immunology / Q000378:metabolism; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004789:Enzyme Activation; D007136:Immunoglobulins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D018121:Receptors, Cytokine / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; D016207:Cytokines; D007136:Immunoglobulins; D008070:Lipopolysaccharides; D018121:Receptors, Cytokine; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C410591:Tslpr protein, mouse; C440499:lipopolysaccharide, Escherichia coli O111 B4; D048052:Mitogen-Activated Protein Kinase 3; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse
keywords: Thymic stromal lymphopoietin; acute lung injury; dendritic cells; lipopolysaccharide; thymic stromal lymphopoietin receptor