PMID- 24666695
OWN - NLM
STAT- MEDLINE
DCOM- 20141205
LR  - 20240213
IS  - 1097-6825 (Electronic)
IS  - 0091-6749 (Print)
IS  - 0091-6749 (Linking)
VI  - 134
IP  - 2
DP  - 2014 Aug
TI  - Loss of regulator of G protein signaling 5 promotes airway hyperresponsiveness in 
      the absence of allergic inflammation.
PG  - 451-9
LID - S0091-6749(14)00174-2 [pii]
LID - 10.1016/j.jaci.2014.01.019 [doi]
AB  - BACKGROUND: Although eosinophilic inflammation typifies allergic asthma, it is 
      not a prerequisite for airway hyperresponsiveness (AHR), suggesting that 
      underlying abnormalities in structural cells, such as airway smooth muscle (ASM), 
      contribute to the asthmatic diathesis. Dysregulation of procontractile G 
      protein-coupled receptor (GPCR) signaling in ASM could mediate enhanced 
      contractility. OBJECTIVE: We explored the role of a regulator of procontractile 
      GPCR signaling, regulator of G protein signaling 5 (RGS5), in unprovoked and 
      allergen-induced AHR. METHODS: We evaluated GPCR-evoked Ca(2+) signaling, 
      precision-cut lung slice (PCLS) contraction, and lung inflammation in naive and 
      Aspergillus fumigatus-challenged wild-type and Rgs5(-/-) mice. We analyzed lung 
      resistance and dynamic compliance in live anesthetized mice using invasive 
      plethysmography. RESULTS: Loss of RGS5 promoted constitutive AHR because of 
      enhanced GPCR-induced Ca(2+) mobilization in ASM. PCLSs from naive Rgs5(-/-) mice 
      contracted maximally at baseline independently of allergen challenge. RGS5 
      deficiency had little effect on the parameters of allergic inflammation, 
      including cell counts in bronchoalveolar lavage fluid, mucin production, ASM 
      mass, and subepithelial collagen deposition. Unexpectedly, induced IL-13 and 
      IL-33 levels were much lower in challenged lungs from Rgs5(-/-) mice relative to 
      those seen in wild-type mice. CONCLUSION: Loss of RGS5 confers spontaneous AHR in 
      mice in the absence of allergic inflammation. Because it is selectively expressed 
      in ASM within the lung and does not promote inflammation, RGS5 might be a 
      therapeutic target for asthma.
CI  - Published by Mosby, Inc.
FAU - Balenga, Nariman A
AU  - Balenga NA
AD  - Molecular Signal Transduction Section, Laboratory of Allergic Diseases, National 
      Institute of Allergy and Infectious Diseases/National Institutes of Health, 
      Bethesda, Md.
FAU - Jester, William
AU  - Jester W
AD  - Pulmonary, Allergy and Critical Care Division, Airways Biology Initiative, 
      University of Pennsylvania, Philadelphia, Pa.
FAU - Jiang, Meiqi
AU  - Jiang M
AD  - Pulmonary, Allergy and Critical Care Division, Airways Biology Initiative, 
      University of Pennsylvania, Philadelphia, Pa.
FAU - Panettieri, Reynold A Jr
AU  - Panettieri RA Jr
AD  - Pulmonary, Allergy and Critical Care Division, Airways Biology Initiative, 
      University of Pennsylvania, Philadelphia, Pa.
FAU - Druey, Kirk M
AU  - Druey KM
AD  - Molecular Signal Transduction Section, Laboratory of Allergic Diseases, National 
      Institute of Allergy and Infectious Diseases/National Institutes of Health, 
      Bethesda, Md. Electronic address: kdruey@niaid.nih.gov.
LA  - eng
GR  - P01 HL114471/HL/NHLBI NIH HHS/United States
GR  - ZIA AI000939-10/ImNIH/Intramural NIH HHS/United States
GR  - P30 ES013508/ES/NIEHS NIH HHS/United States
GR  - AI001746/AI/NIAID NIH HHS/United States
GR  - R01 HL097796/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
DEP - 20140322
PL  - United States
TA  - J Allergy Clin Immunol
JT  - The Journal of allergy and clinical immunology
JID - 1275002
RN  - 0 (Allergens)
RN  - 0 (Il33 protein, mouse)
RN  - 0 (Interleukin-13)
RN  - 0 (Interleukin-33)
RN  - 0 (Interleukins)
RN  - 0 (Mucins)
RN  - 0 (RGS Proteins)
RN  - 0 (Rgs5 protein, mouse)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Allergens/administration & dosage/*immunology
MH  - Animals
MH  - Aspergillus fumigatus/immunology
MH  - Bronchoalveolar Lavage Fluid/immunology
MH  - Calcium/*immunology
MH  - Calcium Signaling
MH  - Female
MH  - Gene Expression Regulation
MH  - Injections, Intraperitoneal
MH  - Interleukin-13/genetics/immunology
MH  - Interleukin-33
MH  - Interleukins/genetics/immunology
MH  - Lung/drug effects/immunology/*pathology
MH  - Mice
MH  - Mice, Knockout
MH  - Mucins/immunology
MH  - Muscle Contraction
MH  - Myocytes, Smooth Muscle/immunology/*pathology
MH  - Plethysmography
MH  - RGS Proteins/deficiency/genetics/*immunology
MH  - Respiratory Hypersensitivity/genetics/immunology/*pathology
MH  - Respiratory Mucosa
MH  - Tissue Culture Techniques
PMC - PMC4119844
MID - NIHMS564503
OTO - NOTNLM
OT  - Aspergillus fumigatus
OT  - Asthma
OT  - G proteins
OT  - airway hyperresponsiveness
OT  - regulator of G protein signaling proteins
EDAT- 2014/03/29 06:00
MHDA- 2014/12/15 06:00
PMCR- 2015/08/01
CRDT- 2014/03/27 06:00
PHST- 2013/05/10 00:00 [received]
PHST- 2014/01/24 00:00 [revised]
PHST- 2014/01/27 00:00 [accepted]
PHST- 2014/03/27 06:00 [entrez]
PHST- 2014/03/29 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
PHST- 2015/08/01 00:00 [pmc-release]
AID - S0091-6749(14)00174-2 [pii]
AID - 10.1016/j.jaci.2014.01.019 [doi]
PST - ppublish
SO  - J Allergy Clin Immunol. 2014 Aug;134(2):451-9. doi: 10.1016/j.jaci.2014.01.019. 
      Epub 2014 Mar 22.