Bradykinin increases the in vivo expression of the CXC chemokine receptors CXCR1 and CXCR2 in patients with allergic rhinitis.
BACKGROUND
Increased levels of bradykinin and IL-8 have been detected within the airways of individuals with active symptoms of allergic rhinitis and asthma.


OBJECTIVE
We sought to investigate the in vivo effect of bradykinin on the expression of the IL-8 receptors CXCR1 and CXCR2 in nasal cells.


METHODS
Nasal samples were obtained from patients with active allergic rhinitis; patients with mild, quiescent allergic rhinitis; and healthy control subjects. CXCR1 and CXCR2 mRNA expression in the nasal cells was measured by means of quantitative real-time RT-PCR in baseline samples from all subjects, as well as in samples obtained after in vivo bradykinin challenge in healthy control subjects and patients with mild allergic rhinitis. CXCR1 and CXCR2 cell-surface expression was also assessed by means of flow cytometry in nasal epithelial cells at baseline and after ex vivo bradykinin challenge.


RESULTS
No difference was seen in CXCR1 or CXCR2 mRNA expression between healthy control subjects and patients with quiescent allergic rhinitis at baseline; however, patients with active allergic rhinitis had increased baseline expression of both CXCR1 and CXCR2 mRNA. In vivo nasal bradykinin challenge significantly increased CXCR1 and CXCR2 mRNA expression in patients with quiescent allergic rhinitis but had no effect in healthy control subjects. Low levels of CXCR1 but not CXCR2 cell-surface expression was detected in nasal epithelial cells at baseline, and ex vivo bradykinin challenge induced CXCR2 cell-surface expression in nasal epithelial cells from patients with mild allergic rhinitis.


CONCLUSIONS
This study demonstrates the in vivo regulation of chemokine receptors by means of bradykinin in human airway tissue in patients with allergic rhinitis.
Eddleston
Jane
J
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, Calif 92037, USA.
Christiansen
Sandra C
SC
Jenkins
Gavin R
GR
Koziol
James A
JA
Zuraw
Bruce L
BL
D001920:Bradykinin / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology*; D009297:Nasal Mucosa / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D023062:Receptors, Interleukin-8A / Q000235:genetics*; D023063:Receptors, Interleukin-8B / Q000235:genetics*; D012221:Rhinitis, Allergic, Perennial / Q000235:genetics*
D018836:Inflammation Mediators; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; D001920:Bradykinin