Stephen P Hunt

Publications (2)3.11 Total impact

• Source

  Available from: James P Stewart

  Article: Altered host response to murine gammaherpesvirus 68 infection in mice lacking the tachykinin 1 gene and the receptor for substance P.

  John P Quinn, Anja Kipar, David J Hughes, Elaine Bennett, Helen Cox, Lynn McLaughlin, Andreas Zimmer, Stephen P Hunt, James P Stewart
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  ABSTRACT: The tachykinins are implicated in neurogenic inflammation and the neuropeptide substance P in particular has been shown to be a proinflammatory mediator. A role for the tachykinins in host response to viral infection has been previously demonstrated using either TAC1- or NK1 receptor-deficient transgenic mice. However, due to redundancy in the peptide-receptor complexes we wished determine whether a deficiency in TAC1 and NK1(R) in combination exhibited an enhanced phenotype. TAC1 and NK1(R)-deficient mice were therefore crossed to generate transgenic mice in both (NK1(-/-)×TAC1(-/-)). As expected, after infection with the respiratory pathogen murine gammaherpesvirus (MHV-68), TAC1 and NK1(R)-deficient mice were more susceptible to infection than wild-type C57BL/6 controls. However, unexpectedly, NK1(-/-)×TAC1(-/-) mice were more resistant to infection arguing for a lack of feedback inhibition through alternative receptors in these mice. Histopathological examination did not show any great differences in the inflammatory responses between groups of infected animals, except for the presence of focal perivascular B cell accumulations in lungs of all the knockout mice. These were most pronounced in the NK1(-/-)×TAC1(-/-) mice. These results confirm an important role for TAC1 and NK1(R) in the control of viral infection but reinforce the complex nature of the peptide-receptor interactions.
  Neuropeptides 02/2011; 45(1):49-53. · 1.55 Impact Factor
• Source

  Available from: James P Stewart

  Article: Involvement of preprotachykinin A gene-encoded peptides and the neurokinin 1 receptor in endotoxin-induced murine airway inflammation.

  Zsuzsanna Helyes, Krisztián Elekes, Katalin Sándor, István Szitter, László Kereskai, Erika Pintér, Agnes Kemény, János Szolcsányi, Lynn McLaughlin, Sylvia Vasiliou, Anja Kipar, Andreas Zimmer, Stephen P Hunt, James P Stewart, John P Quinn
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  ABSTRACT: Tachykinins encoded by the preprotachykinin A (TAC1) gene such as substance P (SP) and neurokinin A (NKA) are involved in neurogenic inflammatory processes via predominantly neurokinins 1 and 2 (NK1 and NK2) receptor activation, respectively. Endokinins and hemokinins encoded by the TAC4 gene also have remarkable selectivity and potency for the NK1 receptors and might participate in inflammatory cell functions. The aim of the present study was to investigate endotoxin-induced airway inflammation and consequent bronchial hyper-reactivity in TAC1(-/-), NK1(-/-) and also in double knockout (TAC1(-/-)/NK1(-/-)) mice. Sub-acute interstitial lung inflammation was evoked by intranasal Escherichia coli lipopolysaccharide (LPS) in the knockout mice and their wildtype C57BL/6 counterparts 24 h before measurement. Respiratory parameters were measured with unrestrained whole body plethysmography. Bronchoconstriction was induced by inhalation of the muscarinic receptor agonist carbachol and Penh (enhanced pause) correlating with airway resistance was calculated. Lung interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) concentrations were measured with ELISA. Histological evaluation was performed and a composite morphological score was determined. Myeloperoxidase (MPO) activity in the lung was measured with spectrophotometry to quantify the number of infiltrating neutrophils/macrophages. Airway hyper-reactivity was significantly reduced in the TAC1(-/-) as well as the TAC1(-/-)/NK1(-/-) groups. However, LPS-induced histological inflammatory changes (perivascular/peribronchial oedema, neutrophil infiltration and goblet cell hyperplasia), MPO activity and TNF-alpha concentration were markedly diminished only in TAC1(-/-) mice. Interestingly, the concentrations of both cytokines, IL-1beta and TNF-alpha, were significantly greater in the NK1(-/-) group. These data clearly demonstrated on the basis of histology, MPO and cytokine measurements that TAC1 gene-derived tachykinins, SP and NKA, play a significant role in the development of endotoxin-induced murine airway inflammation, but not solely via NK1 receptor activation. However, in inflammatory bronchial hyper-responsiveness other tachykinins, such as hemokinin-1 acting through NK1 receptors also might be involved.
  Neuropeptides 10/2010; 44(5):399-406. · 1.55 Impact Factor