Modulation of eotaxin-3 (CCL26) in alveolar type II epithelial cells.
Airway epithelial inflammation associated with emphysema, chronic bronchitis, chronic obstructive pulmonary disease (COPD) and asthma is regulated in part by alveolar type II cell chemokine signaling. Data suggest that resident lung cells use CCR3, CCR5 and CCR2 chemokine receptor/ligand systems to regulate the profile of leukocytes recruited in disease-associated inflammatory conditions. Thus studies were designed to test whether alveolar type II cells possess a Th1-activated CCR5-ligand system that modulates the Th2-activated CCR3/eotaxin-2 (CCL24), eotaxin-3 (CCL26) chemokine systems. The A549 alveolar type II epithelial-like cell culture model was used to demonstrate that alveolar type II cells constitutively express CCR5 which may be upregulated by MIP-1alpha (CCL3) whose expression was induced by the Th1 cytokines IL-1beta and IFN-gamma. Selective down-regulation of CCL26, but not CCL24, was observed in CCL3 and IL-4/CCL3 stimulated cells. Down-regulation was reversed by anti-CCR5 neutralizing antibody treatment. Thus, one mechanism through which Th1-activated CCCR5/ligand pathways modulate Th2-activated CCR3/ligand pathways is the differential down-regulation of CCL26 expression. Results suggest that the CCR3 and CCR5 receptor/ligand signaling pathways may be important targets for development of novel mechanism-based adjunctive therapies designed to abrogate the chronic inflammation associated with airway diseases.
Abonyo
Barack O
BO
Florida A & M University, College of Pharmacy and Pharmaceutical Sciences, Tallahassee, FL 32307, USA. abonyo.barack@famu.edu
Lebby
Kimberly D
KD
Tonry
Jessica H
JH
Ahmad
Munir
M
Heiman
Ann S
AS
D045744:Cell Line, Tumor; D000075906:Chemokine CCL26; D054405:Chemokine CCL3; D019742:Chemokines, CC / Q000276:immunology / Q000378:metabolism*; D004847:Epithelial Cells / Q000276:immunology*; D006801:Humans; D015847:Interleukin-4 / Q000276:immunology; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000276:immunology*; D019713:Receptors, CCR5 / Q000276:immunology / Q000378:metabolism
C120429:CCL26 protein, human; C515429:CCL3 protein, human; D000075906:Chemokine CCL26; D054405:Chemokine CCL3; D019742:Chemokines, CC; D019713:Receptors, CCR5; D015847:Interleukin-4