title: IL-25 regulates the expression of adhesion molecules on eosinophils: mechanism of eosinophilia in allergic inflammation.
abstract: BACKGROUND
  Interleukin-25 (IL-25) is a novel T-helper-2 (Th2) cytokine of the IL-17 family that plays a key role in allergic inflammation. Recent studies reported that over-expression of IL-25 in mouse induces eosinophilia. We investigated the effect of IL-25 on the expression of several adhesion molecules on human eosinophils and the underlying intracellular mechanisms.
  
  
  METHODS
  Viability of eosinophils was measured by annexin V-fluorescein isothiocyanate (FITC) assay. Gene expression and surface expression of intercellular adhesion molecule (ICAM)-1 (CD54), ICAM-3 (CD50), L-selectin (CD62L), leukocyte function-associated antigen (LFA-1) (CD11a/CD18) and very late antigen-4 (VLA-4, CD49d/CD29) on eosinophils were measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometry, respectively. Adhesion of eosinophils to fibronectin was assessed using the fibronectin-coated insert system.
  
  
  RESULTS
  Viability of eosinophils was significantly enhanced by IL-25 from 41% to 76% dose-dependently. IL-25 could significantly upregulate the surface expression of ICAM-1, but suppress those of ICAM-3 and L-selectin on eosinophils in a dose-dependent manner. Adhesion of eosinophils to fibronectin was also significantly enhanced by IL-25. Besides, pre-incubation with p38 mitogen-activated protein kinases (MAPK) inhibitor SB203580, C-Jun NH2-terminal protein kinases (JNK) inhibitor SP600125 and proteosome inhibitor MG-132 could significantly restrain the effects of IL-25 on surface expression of L-selectin, ICAM-1 and ICAM-3, respectively, and also on the adhesion of eosinophils onto fibronectin (all P < 0.05).
  
  
  CONCLUSIONS
  Our findings suggest an essential role of IL-25 in enhancing survival and regulating surface expression of ICAM-1, ICAM-3 and L-selectin on human eosinophils through the activation of p38 MAPK, JNK and nuclear factor (NF)-kappaB pathways, thereby shedding light on the molecular mechanisms of IL-25-induced eosinophilia in allergic inflammation.
authors.affiliation: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, NT, Hong Kong.
authors.forename: P F Y
authors.initials: PF
authors.lastname: Cheung
authors.forename: C K
authors.initials: CK
authors.lastname: Wong
authors.forename: W K
authors.initials: WK
authors.lastname: Ip
authors.forename: C W K
authors.initials: CW
authors.lastname: Lam
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004802:Eosinophilia / Q000276:immunology; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D007093:Imidazoles / Q000494:pharmacology; D007249:Inflammation / Q000276:immunology; D020381:Interleukin-17; D007378:Interleukins / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000276:immunology; D007976:Leupeptins / Q000494:pharmacology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000276:immunology; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000276:immunology
chemical_list: D015815:Cell Adhesion Molecules; D015853:Cysteine Proteinase Inhibitors; D004791:Enzyme Inhibitors; C486701:IL25 protein, human; D007093:Imidazoles; D020381:Interleukin-17; D007378:Interleukins; D007976:Leupeptins; D016328:NF-kappa B; D011725:Pyridines; D012333:RNA, Messenger; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde