Influenza A infection attenuates relaxation responses of mouse tracheal smooth muscle evoked by acrolein

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    Abstract

    The airway epithelium is an important source of relaxant mediators, and damage to the epithelium caused by respiratory tract viruses may contribute to airway hyperreactivity. The aim of this study was to determine whether influenza A-induced epithelial damage would modulate relaxation responses evoked by acrolein, a toxic and prevalent component of smoke. Male BALB/c mice were inoculated intranasally with influenza A/PR-8/34 (VIRUS-infected) or allantoic fluid (SHAM-infected). On day 4 post-inoculation, isometric tension recording studies were conducted on carbachol pre-contracted tracheal segments isolated from VIRUS and SHAM mice. Relaxant responses to acrolein (30 μM) were markedly smaller in VIRUS segments compared to SHAM segments (2 ± 1% relaxation vs. 28 ± 5%, n = 14, p < 0.01). Similarly, relaxation responses of VIRUS segments to the neuropeptide substance P (SP) were greatly attenuated (1 ± 1% vs. 47 ± 6% evoked by 1 nM SP, n = 14, p < 0.001). Consistent with epithelial damage, PGE2 release in response to both acrolein and SP were reduced in VIRUS segments (>35% reduction, n = 6, p < 0.01), as determined using ELISA. In contrast, exogenous PGE2 was 2.8-fold more potent in VIRUS relative to SHAM segments (−log EC50 7.82 ± 0.14 vs. 7.38 ± 0.05, n = 7, p < 0.01) whilst responses of VIRUS segments to the β-adrenoceptor agonist isoprenaline were similar to SHAM segments. In conclusion, relaxation responses evoked by acrolein were profoundly diminished in tracheal segments isolated from influenza A-infected mice. The mechanism through which influenza A infection attenuates this response appears to involve reduced production of PGE2 in response to SP due to epithelial cell loss, and may provide insight into the airway hyperreactivity observed with influenza A infection.
    Original languageEnglish
    Pages (from-to)519–526
    Number of pages8
    JournalBiochemical Pharmacology
    Volume93
    Issue number4
    DOIs
    Publication statusPublished - 15 Feb 2015

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    Acrolein
    Human Influenza
    Smooth Muscle
    Muscle
    Infection
    Dinoprostone
    Epithelium
    Poisons
    Carbachol
    Viruses
    Isoproterenol
    Smoke
    Respiratory System
    Adrenergic Receptors
    Epithelial Cells
    Enzyme-Linked Immunosorbent Assay
    salicylhydroxamic acid
    Fluids

    Cite this

    @article{f2ddbe6b15804fd1b492f9366da89f18,
    title = "Influenza A infection attenuates relaxation responses of mouse tracheal smooth muscle evoked by acrolein",
    abstract = "The airway epithelium is an important source of relaxant mediators, and damage to the epithelium caused by respiratory tract viruses may contribute to airway hyperreactivity. The aim of this study was to determine whether influenza A-induced epithelial damage would modulate relaxation responses evoked by acrolein, a toxic and prevalent component of smoke. Male BALB/c mice were inoculated intranasally with influenza A/PR-8/34 (VIRUS-infected) or allantoic fluid (SHAM-infected). On day 4 post-inoculation, isometric tension recording studies were conducted on carbachol pre-contracted tracheal segments isolated from VIRUS and SHAM mice. Relaxant responses to acrolein (30 μM) were markedly smaller in VIRUS segments compared to SHAM segments (2 ± 1{\%} relaxation vs. 28 ± 5{\%}, n = 14, p < 0.01). Similarly, relaxation responses of VIRUS segments to the neuropeptide substance P (SP) were greatly attenuated (1 ± 1{\%} vs. 47 ± 6{\%} evoked by 1 nM SP, n = 14, p < 0.001). Consistent with epithelial damage, PGE2 release in response to both acrolein and SP were reduced in VIRUS segments (>35{\%} reduction, n = 6, p < 0.01), as determined using ELISA. In contrast, exogenous PGE2 was 2.8-fold more potent in VIRUS relative to SHAM segments (−log EC50 7.82 ± 0.14 vs. 7.38 ± 0.05, n = 7, p < 0.01) whilst responses of VIRUS segments to the β-adrenoceptor agonist isoprenaline were similar to SHAM segments. In conclusion, relaxation responses evoked by acrolein were profoundly diminished in tracheal segments isolated from influenza A-infected mice. The mechanism through which influenza A infection attenuates this response appears to involve reduced production of PGE2 in response to SP due to epithelial cell loss, and may provide insight into the airway hyperreactivity observed with influenza A infection.",
    author = "Esther Cheah and Tracy Mann and Philip Burcham and Peter Henry",
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    language = "English",
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    Influenza A infection attenuates relaxation responses of mouse tracheal smooth muscle evoked by acrolein. / Cheah, Esther; Mann, Tracy; Burcham, Philip; Henry, Peter.

    In: Biochemical Pharmacology, Vol. 93, No. 4, 15.02.2015, p. 519–526.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Influenza A infection attenuates relaxation responses of mouse tracheal smooth muscle evoked by acrolein

    AU - Cheah, Esther

    AU - Mann, Tracy

    AU - Burcham, Philip

    AU - Henry, Peter

    PY - 2015/2/15

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    N2 - The airway epithelium is an important source of relaxant mediators, and damage to the epithelium caused by respiratory tract viruses may contribute to airway hyperreactivity. The aim of this study was to determine whether influenza A-induced epithelial damage would modulate relaxation responses evoked by acrolein, a toxic and prevalent component of smoke. Male BALB/c mice were inoculated intranasally with influenza A/PR-8/34 (VIRUS-infected) or allantoic fluid (SHAM-infected). On day 4 post-inoculation, isometric tension recording studies were conducted on carbachol pre-contracted tracheal segments isolated from VIRUS and SHAM mice. Relaxant responses to acrolein (30 μM) were markedly smaller in VIRUS segments compared to SHAM segments (2 ± 1% relaxation vs. 28 ± 5%, n = 14, p < 0.01). Similarly, relaxation responses of VIRUS segments to the neuropeptide substance P (SP) were greatly attenuated (1 ± 1% vs. 47 ± 6% evoked by 1 nM SP, n = 14, p < 0.001). Consistent with epithelial damage, PGE2 release in response to both acrolein and SP were reduced in VIRUS segments (>35% reduction, n = 6, p < 0.01), as determined using ELISA. In contrast, exogenous PGE2 was 2.8-fold more potent in VIRUS relative to SHAM segments (−log EC50 7.82 ± 0.14 vs. 7.38 ± 0.05, n = 7, p < 0.01) whilst responses of VIRUS segments to the β-adrenoceptor agonist isoprenaline were similar to SHAM segments. In conclusion, relaxation responses evoked by acrolein were profoundly diminished in tracheal segments isolated from influenza A-infected mice. The mechanism through which influenza A infection attenuates this response appears to involve reduced production of PGE2 in response to SP due to epithelial cell loss, and may provide insight into the airway hyperreactivity observed with influenza A infection.

    AB - The airway epithelium is an important source of relaxant mediators, and damage to the epithelium caused by respiratory tract viruses may contribute to airway hyperreactivity. The aim of this study was to determine whether influenza A-induced epithelial damage would modulate relaxation responses evoked by acrolein, a toxic and prevalent component of smoke. Male BALB/c mice were inoculated intranasally with influenza A/PR-8/34 (VIRUS-infected) or allantoic fluid (SHAM-infected). On day 4 post-inoculation, isometric tension recording studies were conducted on carbachol pre-contracted tracheal segments isolated from VIRUS and SHAM mice. Relaxant responses to acrolein (30 μM) were markedly smaller in VIRUS segments compared to SHAM segments (2 ± 1% relaxation vs. 28 ± 5%, n = 14, p < 0.01). Similarly, relaxation responses of VIRUS segments to the neuropeptide substance P (SP) were greatly attenuated (1 ± 1% vs. 47 ± 6% evoked by 1 nM SP, n = 14, p < 0.001). Consistent with epithelial damage, PGE2 release in response to both acrolein and SP were reduced in VIRUS segments (>35% reduction, n = 6, p < 0.01), as determined using ELISA. In contrast, exogenous PGE2 was 2.8-fold more potent in VIRUS relative to SHAM segments (−log EC50 7.82 ± 0.14 vs. 7.38 ± 0.05, n = 7, p < 0.01) whilst responses of VIRUS segments to the β-adrenoceptor agonist isoprenaline were similar to SHAM segments. In conclusion, relaxation responses evoked by acrolein were profoundly diminished in tracheal segments isolated from influenza A-infected mice. The mechanism through which influenza A infection attenuates this response appears to involve reduced production of PGE2 in response to SP due to epithelial cell loss, and may provide insight into the airway hyperreactivity observed with influenza A infection.

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