Double-stranded RNA increases kinin B1 receptor expression and function in human airway epithelial cells.
Increased levels of kinins have been detected within the airways during upper respiratory viral infections (URIs). Rhinovirus, the major URI associated with acute exacerbations of asthma, is an ssRNA virus that primarily infects the airway epithelium and produces dsRNA during replication. We asked whether dsRNA could increase the expression of kinin receptors in airway epithelial cells, thereby potentiating the inflammatory consequences of kinin generation. Human airway epithelial cell line BEAS-2B was stimulated with the dsRNA analog Poly I:C and kinin receptor expression detected by quantitative RT-PCR as well as radioligand binding. Poly I:C induced an increase in B1 and B2 receptor mRNA levels in BEAS-2B and primary human normal bronchial epithelial cells. At the cell surface, only B1 receptor expression was increased by Poly I:C. Furthermore, pretreatment of BEAS-2B cells with Poly I:C enhanced the induction of phospho-ERK following B1 receptor ligand stimulation. To investigate whether these finding had potential in vivo relevance, we assessed B1 receptor expression in nasal tissue obtained from 8 normal human subjects with URIs and 3 control subjects. Five of the URI subjects demonstrated increased B1 receptor mRNA compared to the 3 control subjects. We suggest that increased expression of B1 receptor in the human airway following a URI could increase the risk of an exacerbation of asthma by contributing to increased inflammation in the airway.
Veterans Affairs Medical Center, San Diego, CA, USA.
S H
SH
Bengtson
J
J
Eddleston
S C
SC
Christiansen
B L
BL
Zuraw
D001980:Bronchi / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D010850:Picornaviridae Infections / Q000378:metabolism / Q000821:virology; D011070:Poly I-C / Q000494:pharmacology; D012330:RNA, Double-Stranded / Q000494:pharmacology / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D043783:Receptor, Bradykinin B1 / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D043782:Receptor, Bradykinin B2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism*; D012141:Respiratory Tract Infections / Q000378:metabolism / Q000821:virology; D012229:Rhinovirus / Q000378:metabolism; D015854:Up-Regulation
D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D048049:Extracellular Signal-Regulated MAP Kinases; D011070:Poly I-C