IL-25 regulates the expression of adhesion molecules on eosinophils: mechanism of eosinophilia in allergic inflammation

Allergy. 2006 Jul;61(7):878-85. doi: 10.1111/j.1398-9995.2006.01102.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Cell Adhesion / drug effects
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / immunology*
  • Cell Adhesion Molecules / metabolism
  • Cells, Cultured
  • Cysteine Proteinase Inhibitors / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Eosinophilia / immunology
  • Eosinophils / drug effects*
  • Eosinophils / immunology
  • Eosinophils / metabolism
  • Gene Expression Regulation / drug effects
  • Humans
  • Hypersensitivity / immunology
  • Imidazoles / pharmacology
  • Inflammation / immunology
  • Interleukin-17
  • Interleukins / pharmacology*
  • JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • JNK Mitogen-Activated Protein Kinases / immunology
  • Leupeptins / pharmacology
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / immunology
  • Pyridines / pharmacology
  • RNA, Messenger / metabolism
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / immunology


  • Cell Adhesion Molecules
  • Cysteine Proteinase Inhibitors
  • Enzyme Inhibitors
  • IL25 protein, human
  • Imidazoles
  • Interleukin-17
  • Interleukins
  • Leupeptins
  • NF-kappa B
  • Pyridines
  • RNA, Messenger
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • SB 203580
  • benzyloxycarbonylleucyl-leucyl-leucine aldehyde