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Expression and activation of the oxytocin receptor in airway smooth muscle cells: Regulation by TNFalpha and IL-13.
- Source :
-
Respiratory research [Respir Res] 2010 Jul 29; Vol. 11, pp. 104. Date of Electronic Publication: 2010 Jul 29. - Publication Year :
- 2010
-
Abstract
- 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.<br />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.<br />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.<br />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.
- Subjects :
- Adult
Animals
Asthma immunology
Asthma physiopathology
Bronchoalveolar Lavage Fluid chemistry
Bronchoconstriction
Bronchodilator Agents pharmacology
Calcium Signaling
Case-Control Studies
Cells, Cultured
Enzyme-Linked Immunosorbent Assay
Female
Flow Cytometry
Fluorometry
Forced Expiratory Volume
Humans
Lung drug effects
Lung immunology
Lung physiopathology
Male
Mice
Mice, Inbred BALB C
Middle Aged
Myocytes, Smooth Muscle drug effects
Myocytes, Smooth Muscle immunology
RNA, Messenger metabolism
Receptors, Oxytocin genetics
Reverse Transcriptase Polymerase Chain Reaction
Time Factors
Trachea drug effects
Trachea immunology
Trachea physiopathology
Up-Regulation
Vital Capacity
Young Adult
Asthma metabolism
Interleukin-13 metabolism
Lung metabolism
Myocytes, Smooth Muscle metabolism
Oxytocin metabolism
Receptors, Oxytocin metabolism
Trachea metabolism
Tumor Necrosis Factor-alpha metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1465-993X
- Volume :
- 11
- Database :
- MEDLINE
- Journal :
- Respiratory research
- Publication Type :
- Academic Journal
- Accession number :
- 20670427
- Full Text :
- https://doi.org/10.1186/1465-9921-11-104