Long-term induction of beta-CGRP mRNA in rat lungs by allergic inflammation.
Calcitonin gene-related peptide (CGRP) is one of the major neuropeptides released from sensory nerve endings and neuroendocrine cells of the lung. Two CGRP isoforms, alpha-and beta-CGRP, have been identified in rats and humans, but no studies have attempted to reveal direct evidence of differences in action or location of these isoforms in allergic inflammation (AI). We investigated mRNA expressions of alpha-and beta-CGRP in lungs, nodose ganglia (NG), and dorsal root ganglia (DRG) of an animal model for AI of the airways, utilizing a model created by sensitizing Brown Norway (BN) rats with ovalbumin (OVA). By semiquantitative RT-PCR analysis, long-lasting enhanced expression of the beta-CGRP mRNA was shown in the lungs of the AI rats (14.5-fold enhancement at 6 hr, 8.1-fold at 24 hr, and 3.7-fold at 120 hr after OVA-challenge compared to the level in the lungs of phosphate-buffered saline (PBS)-challenged control rats). In contrast, the mRNA expression of the alpha-CGRP in AI lungs showed only a transient increase after OVA-challenge (2.7-fold at 6 hr) followed by a lower level of expression (0.5-fold at 48 hr and 0.6-fold at 120 hr). The mRNA expressions of both isoforms in NG, but not in DRG, were transiently up-regulated at 6 hr after antigen challenge. In situ RT-PCR in combination with immunohistochemical analysis revealed that beta-CGRP was expressed in neuroendocrine cells in clusters (termed neuroepithelial bodies [NEBs]) in AI lungs. These results indicate that the long-term induction of beta-CGRP in NEBs may play an important role in pulmonary AI such as bronchial asthma.
Tsukiji
Jun
J
Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. jtsukiji@yokohama-cu.ac.jp
Sango
Kazunori
K
Udaka
Naoko
N
Kageyama
Haruaki
H
Ito
Takaaki
T
Saito
Haruhiro
H
Horie
Hidenori
H
Inoue
Shuji
S
Kitamura
Hitoshi
H
Hagiwara
Eri
E
Ikeda
Hirotada
H
Okubo
Takao
T
Ishigatsubo
Yoshiaki
Y
D000485:Allergens / Q000276:immunology; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis*; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000378:metabolism; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008297:Male; D009620:Nodose Ganglion / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D011914:Rats, Inbred BN; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D000485:Allergens; D012333:RNA, Messenger; D015740:Calcitonin Gene-Related Peptide