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IL‐4 Induced Expression of CCL26 (Eotaxin‐3) mRNA and Protein in Monocytic Cells
Author(s) -
Stubbs Victoria E. L.,
Patel Kamala D.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a203-a
Subject(s) - ccl11 , eotaxin , chemokine , chemokine receptor , chemistry , microbiology and biotechnology , ccr3 , receptor , biology , biochemistry
CCL26/Eotaxin‐3, a member of the CC chemokine family, is an agonist for chemokine receptor CCR3. Published data have recently shown that CCL26 also acts as an antagonist for CCR1, CCR2 and CCR5, unlike other members of the eotaxin family (CCL11/Eotaxin and CCL24/Eotaxin‐2). During inflammation, recruited cells such as monocytes and eosinophils are important sources of chemokines and these cells also possess the receptors acted on by CCL26. Upregulation of CCL26 by IL‐4 has been shown to be STAT6 dependent in human fibroblasts, as well as in intestinal and airway epithelial cells. Using real time PCR techniques, we have shown that IL‐4 induces expression of CCL26 mRNA in human monocytes, monocyte‐derived macrophages and U937 cells; however, CCL26 mRNA expression was not induced by other pro‐inflammatory cytokines such as IFNγ, TNFα or IL‐1β. As expected, IL‐4 stimulation of these cells resulted in time dependent phosphorylation of STAT6. IL‐4 also induced concentration and time dependent secretion of CCL26 in U937 cells. Furthermore, IL‐4 acted synergistically with TNFα and IL‐1β resulting in elevated levels of CCL26 secretion, while co‐stimulation of IL‐4 with IFNγ attenuated CCL26 secretion. Interestingly, the levels of CCL26 mRNA and CCL26 release in cells pre‐treated with IFNgamma; prior to IL‐4 stimulation were reduced, suggesting that IFNγ acts as a negative regulator of IL‐4 induced CCL26 gene expression. These data demonstrate that modulation of CCL26 expression is different from other members of the eotaxin family. Collectively the data suggest that CCL26 plays a distinct biological role in allergic and bowel inflammation. The Alzheimer Society of Canada and the CIHR Institute of Ageing jointly fund this project