Substance P activates both contractile and inflammatory pathways in lymphatics through the neurokinin receptors NK1R and NK3R
Identifieur interne : 004025 ( Ncbi/Checkpoint ); précédent : 004024; suivant : 004026Substance P activates both contractile and inflammatory pathways in lymphatics through the neurokinin receptors NK1R and NK3R
Auteurs : Sanjukta Chakraborty [États-Unis] ; Zhanna Nepiyushchikh [États-Unis] ; Michael J. Davis [États-Unis] ; David C. Zawieja [États-Unis] ; Mariappan Muthuchamy [États-Unis]Source :
- Microcirculation (New York, N.Y. : 1994) [ 1073-9688 ] ; 2011.
Abstract
The aim of this study was to elucidate the molecular signaling mechanisms by which substance P (SP) modulates lymphatic muscle contraction and to determine whether SP stimulates both contractile as well as inflammatory pathways in the lymphatics.
A rat mesenteric lymphatic muscle cell culture model (RMLMCs) and known specific pharmacological inhibitors were utilized to delineate SP mediated signaling pathways in lymphatics.
We detected expression of neurokinin receptor 1 (NK1R) and neurokinin receptor 3 (NK3R) in RMLMCs. SP stimulation increased phosphorylation of myosin light chain 20 (MLC20) as well as p38 mitogen associated protein kinase (p38-MAPK) and extracellular signal regulated kinase (ERK1/2) indicating activation of both a contractile and a pro-inflammatory MAPK pathway. Pharmacological inhibition of both NK1R and NK3R significantly affected the downstream SP signaling. We further examined whether there was any crosstalk between the two pathways upon SP stimulation. Inhibition of ERK1/2 decreased levels of p-MLC20 after SP activation, in a PKC dependent manner, indicating a potential crosstalk between these two pathways.
These data provide the first evidence that SP mediated crosstalk between pro-inflammatory and contractile signaling mechanisms exists in the lymphatic system and may be an important bridge between lymphatic function modulation and inflammation.
Url:
DOI: 10.1111/j.1549-8719.2010.00064.x
PubMed: 21166923
PubMed Central: 3058475
Affiliations:
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Davis</name><affiliation wicri:level="2"><nlm:aff id="A2"> Department of Medical Pharmacology & Physiology, University of Missouri School of Medicine, Columbia, MO</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Missouri (État)</region></placeName><wicri:cityArea> Department of Medical Pharmacology & Physiology, University of Missouri School of Medicine, Columbia</wicri:cityArea></affiliation></author><author><name sortKey="Zawieja, David C" sort="Zawieja, David C" uniqKey="Zawieja D" first="David C." last="Zawieja">David C. Zawieja</name><affiliation wicri:level="2"><nlm:aff id="A1"> Department of Systems Biology and Translational Medicine, Cardiovascular Research Institute, Division of Lymphatic Biology, Texas A&M Health Science Center College of Medicine, 336 Reynolds Medical Building, College Station, TX</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea> Department of Systems Biology and Translational Medicine, Cardiovascular Research Institute, Division of Lymphatic Biology, Texas A&M Health Science Center College of Medicine, 336 Reynolds Medical Building, College Station</wicri:cityArea></affiliation></author><author><name sortKey="Muthuchamy, Mariappan" sort="Muthuchamy, Mariappan" uniqKey="Muthuchamy M" first="Mariappan" last="Muthuchamy">Mariappan Muthuchamy</name><affiliation wicri:level="2"><nlm:aff id="A1"> Department of Systems Biology and Translational Medicine, Cardiovascular Research Institute, Division of Lymphatic Biology, Texas A&M Health Science Center College of Medicine, 336 Reynolds Medical Building, College Station, TX</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea> Department of Systems Biology and Translational Medicine, Cardiovascular Research Institute, Division of Lymphatic Biology, Texas A&M Health Science Center College of Medicine, 336 Reynolds Medical Building, College Station</wicri:cityArea></affiliation></author></analytic><series><title level="j">Microcirculation (New York, N.Y. : 1994)</title><idno type="ISSN">1073-9688</idno><idno type="eISSN">1549-8719</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="S1"><title>Objective</title><p id="P1">The aim of this study was to elucidate the molecular signaling mechanisms by which substance P (SP) modulates lymphatic muscle contraction and to determine whether SP stimulates both contractile as well as inflammatory pathways in the lymphatics.</p></sec><sec sec-type="methods" id="S2"><title>Methods</title><p id="P2">A rat mesenteric lymphatic muscle cell culture model (RMLMCs) and known specific pharmacological inhibitors were utilized to delineate SP mediated signaling pathways in lymphatics.</p></sec><sec id="S3"><title>Results</title><p id="P3">We detected expression of neurokinin receptor 1 (NK1R) and neurokinin receptor 3 (NK3R) in RMLMCs. SP stimulation increased phosphorylation of myosin light chain 20 (MLC<sub>20</sub>) as well as p38 mitogen associated protein kinase (p38-MAPK) and extracellular signal regulated kinase (ERK1/2) indicating activation of both a contractile and a pro-inflammatory MAPK pathway. Pharmacological inhibition of both NK1R and NK3R significantly affected the downstream SP signaling. We further examined whether there was any crosstalk between the two pathways upon SP stimulation. Inhibition of ERK1/2 decreased levels of p-MLC<sub>20</sub> after SP activation, in a PKC dependent manner, indicating a potential crosstalk between these two pathways.</p></sec><sec id="S4"><title>Conclusions</title><p id="P4">These data provide the first evidence that SP mediated crosstalk between pro-inflammatory and contractile signaling mechanisms exists in the lymphatic system and may be an important bridge between lymphatic function modulation and inflammation.</p></sec></div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Missouri (État)</li><li>Texas</li></region></list><tree><country name="États-Unis"><region name="Texas"><name sortKey="Chakraborty, Sanjukta" sort="Chakraborty, Sanjukta" uniqKey="Chakraborty S" first="Sanjukta" last="Chakraborty">Sanjukta Chakraborty</name></region><name sortKey="Davis, Michael J" sort="Davis, Michael J" uniqKey="Davis M" first="Michael J." last="Davis">Michael J. Davis</name><name sortKey="Muthuchamy, Mariappan" sort="Muthuchamy, Mariappan" uniqKey="Muthuchamy M" first="Mariappan" last="Muthuchamy">Mariappan Muthuchamy</name><name sortKey="Nepiyushchikh, Zhanna" sort="Nepiyushchikh, Zhanna" uniqKey="Nepiyushchikh Z" first="Zhanna" last="Nepiyushchikh">Zhanna Nepiyushchikh</name><name sortKey="Zawieja, David C" sort="Zawieja, David C" uniqKey="Zawieja D" first="David C." last="Zawieja">David C. Zawieja</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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