PMID- 20670427
OWN - NLM
STAT- MEDLINE
DCOM- 20100920
LR  - 20211020
IS  - 1465-993X (Electronic)
IS  - 1465-9921 (Print)
IS  - 1465-9921 (Linking)
VI  - 11
IP  - 1
DP  - 2010 Jul 29
TI  - Expression and activation of the oxytocin receptor in airway smooth muscle cells: 
      Regulation by TNFalpha and IL-13.
PG  - 104
LID - 10.1186/1465-9921-11-104 [doi]
AB  - BACKGROUND: During pregnancy asthma may remain stable, improve or worsen. The 
      factors underlying the deleterious effect of pregnancy on asthma remain unknown. 
      Oxytocin is a neurohypophyseal protein that regulates a number of central and 
      peripheral responses such as uterine contractions and milk ejection. Additional 
      evidence suggests that oxytocin regulates inflammatory processes in other tissues 
      given the ubiquitous expression of the oxytocin receptor. The purpose of this 
      study was to define the role of oxytocin in modulating human airway smooth muscle 
      (HASMCs) function in the presence and absence of IL-13 and TNFalpha, cytokines 
      known to be important in asthma. METHOD: Expression of oxytocin receptor in 
      cultured HASMCs was performed by real time PCR and flow cytomery assays. 
      Responses to oxytocin was assessed by fluorimetry to detect calcium signals while 
      isolated tracheal rings and precision cut lung slices (PCLS) were used to measure 
      contractile responses. Finally, ELISA was used to compare oxytocin levels in the 
      bronchoalveloar lavage (BAL) samples from healthy subjects and those with asthma. 
      RESULTS: PCR analysis demonstrates that OXTR is expressed in HASMCs under basal 
      conditions and that both interleukin (IL)-13 and tumor necrosis factor (TNFalpha) 
      stimulate a time-dependent increase in OXTR expression at 6 and 18 hr. 
      Additionally, oxytocin increases cytosolic calcium levels in fura-2-loaded HASMCs 
      that were enhanced in cells treated for 24 hr with IL-13. Interestingly, TNFalpha 
      had little effect on oxytocin-induced calcium response despite increasing 
      receptor expression. Using isolated murine tracheal rings and PCLS, oxytocin also 
      promoted force generation and airway narrowing. Further, oxytocin levels are 
      detectable in bronchoalveolar lavage (BAL) fluid derived from healthy subjects as 
      well as from those with asthma. CONCLUSION: Taken together, we show that 
      cytokines modulate the expression of functional oxytocin receptors in HASMCs 
      suggesting a potential role for inflammation-induced changes in oxytocin receptor 
      signaling in the regulation of airway hyper-responsiveness in asthma.
FAU - Amrani, Yassine
AU  - Amrani Y
AD  - Pulmonary, Allergy and Critical Care Division, Department of Medicine, University 
      of Pennsylvania, TRL Suite 1200, 125 South 31st Street, Philadelphia, PA 19104, 
      USA. ya26@le.ac.uk
FAU - Syed, Farhat
AU  - Syed F
FAU - Huang, Chris
AU  - Huang C
FAU - Li, Katherine
AU  - Li K
FAU - Liu, Veronica
AU  - Liu V
FAU - Jain, Deepika
AU  - Jain D
FAU - Keslacy, Stefan
AU  - Keslacy S
FAU - Sims, Michael W
AU  - Sims MW
FAU - Baidouri, Hasna
AU  - Baidouri H
FAU - Cooper, Philip R
AU  - Cooper PR
FAU - Zhao, Hengjiang
AU  - Zhao H
FAU - Siddiqui, Salman
AU  - Siddiqui S
FAU - Brightling, Christopher E
AU  - Brightling CE
FAU - Griswold, Don
AU  - Griswold D
FAU - Li, Lily
AU  - Li L
FAU - Panettieri, Reynold A Jr
AU  - Panettieri RA Jr
LA  - eng
GR  - R01 HL081824/HL/NHLBI NIH HHS/United States
GR  - R01 HL077735/HL/NHLBI NIH HHS/United States
GR  - R01 HL080676/HL/NHLBI NIH HHS/United States
GR  - P30 ES013508/ES/NIEHS NIH HHS/United States
GR  - R01 HL064063/HL/NHLBI NIH HHS/United States
GR  - 082265/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100729
PL  - England
TA  - Respir Res
JT  - Respiratory research
JID - 101090633
RN  - 0 (Bronchodilator Agents)
RN  - 0 (Interleukin-13)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Oxytocin)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 50-56-6 (Oxytocin)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Asthma/immunology/*metabolism/physiopathology
MH  - Bronchoalveolar Lavage Fluid/chemistry
MH  - Bronchoconstriction
MH  - Bronchodilator Agents/pharmacology
MH  - Calcium Signaling
MH  - Case-Control Studies
MH  - Cells, Cultured
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Flow Cytometry
MH  - Fluorometry
MH  - Forced Expiratory Volume
MH  - Humans
MH  - Interleukin-13/*metabolism
MH  - Lung/drug effects/immunology/*metabolism/physiopathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Middle Aged
MH  - Myocytes, Smooth Muscle/drug effects/immunology/*metabolism
MH  - Oxytocin/*metabolism
MH  - RNA, Messenger/metabolism
MH  - Receptors, Oxytocin/genetics/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Time Factors
MH  - Trachea/drug effects/immunology/*metabolism/physiopathology
MH  - Tumor Necrosis Factor-alpha/*metabolism
MH  - Up-Regulation
MH  - Vital Capacity
MH  - Young Adult
PMC - PMC2922094
EDAT- 2010/07/31 06:00
MHDA- 2010/09/21 06:00
PMCR- 2010/07/29
CRDT- 2010/07/31 06:00
PHST- 2010/03/22 00:00 [received]
PHST- 2010/07/29 00:00 [accepted]
PHST- 2010/07/31 06:00 [entrez]
PHST- 2010/07/31 06:00 [pubmed]
PHST- 2010/09/21 06:00 [medline]
PHST- 2010/07/29 00:00 [pmc-release]
AID - 1465-9921-11-104 [pii]
AID - 10.1186/1465-9921-11-104 [doi]
PST - epublish
SO  - Respir Res. 2010 Jul 29;11(1):104. doi: 10.1186/1465-9921-11-104.