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IL‐25 regulates the expression of adhesion molecules on eosinophils: mechanism of eosinophilia in allergic inflammation
Author(s) -
Cheung P. F. Y.,
Wong C. K.,
Ip W. K.,
Lam C. W. K.
Publication year - 2006
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/j.1398-9995.2006.01102.x
Subject(s) - microbiology and biotechnology , fibronectin , allergic inflammation , chemistry , intercellular adhesion molecule 1 , cell adhesion molecule , cd18 , intercellular adhesion molecule , cell adhesion , biology , immunology , adhesion , inflammation , flow cytometry , extracellular matrix , integrin alpha m , organic chemistry
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‐flourescein 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 NH 2 ‐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)‐ κ B pathways, thereby shedding light on the molecular mechanisms of IL‐25‐induced eosinophilia in allergic inflammation.