RGD Reference Report - Glucocorticoids ameliorate antigen-induced bronchial smooth muscle hyperresponsiveness by inhibiting upregulation of RhoA in rats. - Rat Genome Database

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Glucocorticoids ameliorate antigen-induced bronchial smooth muscle hyperresponsiveness by inhibiting upregulation of RhoA in rats.

Authors: Chiba, Y  Goto, K  Hirahara, M  Sakai, H  Misawa, M 
Citation: Chiba Y, etal., J Pharmacol Sci. 2008 Apr;106(4):615-25. Epub 2008 Apr 5.
RGD ID: 2298885
Pubmed: PMID:18391481   (View Abstract at PubMed)

To determine the mechanism(s) of the inhibitory effect of glucocorticoids on airway hyperresponsiveness in allergic bronchial asthma, the effects of systemic treatment with glucocorticoids on bronchial smooth muscle hyperresponsiveness and RhoA upregulation were investigated in rats with allergic bronchial asthma. Rats were sensitized and repeatedly challenged with 2,4-dinitrophenylated Ascaris suum antigen. Animals were also treated with prednisolone or beclomethasone (each 10 mg/kg, i.p.) once a day during the antigen inhalation period. Repeated antigen inhalation caused a marked bronchial smooth muscle hyperresponsiveness to acetylcholine with an upregulation of RhoA. Augmented acetylcholine-induced activation of RhoA and phosphorylation of myosin light chain were observed in bronchial smooth muscles of the antigen-exposed animals. Systemic treatment with either glucocorticoid used inhibited the bronchial smooth muscle hypercontraction until the level of the sensitized control rats that received saline inhalation instead of antigen challenge. Interestingly, both glucocorticoids also inhibited the upregulation of RhoA and augmented acetylcholine-induced activation of RhoA and phosphorylation of myosin light chain. In conclusion, glucocorticoids ameliorated the augmented bronchial smooth muscle contraction by inhibiting upregulation of RhoA. These effects of glucocorticoids may account for, in part, their beneficial effects in the treatment of asthma.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
asthma  ISORhoa (Rattus norvegicus)2298885; 2298885 RGD 
asthma  IEP 2298885 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to glucocorticoid  IEP 2298885 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Rhoa  (ras homolog family member A)

Genes (Mus musculus)
Rhoa  (ras homolog family member A)

Genes (Homo sapiens)
RHOA  (ras homolog family member A)


Additional Information