title: Interleukin-22 exacerbates airway inflammation induced by short-term exposure to cigarette smoke in mice.
abstract: OBJECTIVE
  Interleukin-22 (IL-22) exhibits both proinflammatory and anti-inflammatory properties in various biological processes. In this study we explored the effects of exogenous recombinant IL-22 (rIL-22) on cigarette smoke (CS)-induced airway inflammation in mice.
  
  
  METHODS
  Male C57BL/6 mice were divided into groups: (1) CS group exposed to tobacco smoke for 3 consecutive days, (2) rIL-22 group received rIL-22 (100 mg/kg, ip), and (3) CS plus rIL-22 group, received rIL-22 (100 mg/kg, ip) before the CS exposure. The airway resistance (Rn), lung morphology, inflammatory cells in the airways, and inflammatory cytokines and CXCR3 ligands in both bronchoalveolar lavage (BAL) fluids and lung tissues were analyzed.
  
  
  RESULTS
  CS alone significantly elevated IL-22 level in the BAL fluid. Both CS and rIL-22 significantly augmented airway resistance, an influx of inflammatory cells into the airways and lung parenchyma, and significantly elevated levels of pro-inflammatory cytokines (TGFβ1 and IL-17A) and CXCR3 chemokines (particularly CXCL10) at the mRNA and/or protein levels. Furthermore, the effects of rIL-22 on airway resistance and inflammation were synergistic with those of CS, as demonstrated by a further increased Rn value, infiltration of greater numbers of inflammatory cells into the lung, higher levels of inflammatory cytokines and chemokines, and more severe pathological changes in CS plus rIL-22 group as compared to those in CS group.
  
  
  CONCLUSIONS
  Exogenous rIL-22 exacerbates the airway inflammatory responses to CS exposure in part by inducing expression of several proinflammatory cytokines and CXCR3 ligands.
authors.affiliation: Department of Respiratory Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
authors.forename: Jiu-rong
authors.initials: JR
authors.lastname: Li
authors.affiliation: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
authors.forename: Wei-xun
authors.initials: WX
authors.lastname: Zhou
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.
authors.forename: Ke-wu
authors.initials: KW
authors.lastname: Huang
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Respiratory Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
authors.forename: Jin-ming
authors.initials: JM
authors.lastname: Gao
mesh_terms: D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D054357:Chemokine CXCL10 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000378:metabolism; D019570:Inhalation Exposure; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000633:toxicity*; D008024:Ligands; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D054367:Receptors, CXCR3 / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000633:toxicity; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D054357:Chemokine CXCL10; D018836:Inflammation Mediators; D020381:Interleukin-17; D007378:Interleukins; D008024:Ligands; D012333:RNA, Messenger; D054367:Receptors, CXCR3; D011994:Recombinant Proteins; D012906:Smoke; D053773:Transforming Growth Factor beta1; D000097043:Interleukin-22; C114753:CXCL10 protein, human; C515188:Cxcr3 protein, mouse; C098680:Il17a protein, mouse; C508961:Tgfb1 protein, mouse