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Involvement of Capsaicin-Sensitive Lung Vagal Neurons and TRPA1 Receptors in Airway Hypersensitivity Induced by 1,3-β-D-Glucan in Anesthetized Rats.
Int J Mol Sci. 2020 Sep 18; 21(18)IJ

Abstract

Airway exposure to 1,3-β-D-glucan (β-glucan), an essential component of the cell wall of several pathogenic fungi, causes various adverse responses, such as pulmonary inflammation and airway hypersensitivity. The former response has been intensively investigated; however, the mechanism underlying β-glucan-induced airway hypersensitivity is unknown. Capsaicin-sensitive lung vagal (CSLV) afferents are very chemosensitive and stimulated by various insults to the lungs. Activation of CSLV afferents triggers several airway reflexes, such as cough. Furthermore, the sensitization of these afferents is known to contribute to the airway hypersensitivity during pulmonary inflammation. This study was carried out to determine whether β-glucan induces airway hypersensitivity and the role of the CSLV neurons in this hypersensitivity. Our results showed that the intratracheal instillation of β-glucan caused not only a distinctly irregular pattern in baseline breathing, but also induced a marked enhancement in the pulmonary chemoreflex responses to capsaicin in anesthetized, spontaneously breathing rats. The potentiating effect of β-glucan was found 45 min later and persisted at 90 min. However, β-glucan no longer caused the irregular baseline breathing and the potentiating of pulmonary chemoreflex responses after treatment with perineural capsaicin treatment that blocked the conduction of CSLV fibers. Besides, the potentiating effect of β-glucan on pulmonary chemoreflex responses was significantly attenuated by N-acetyl-L-cysteine (a ROS scavenger), HC-030031 (a TRPA1 antagonist), and Laminarin (a Dectin-1 antagonist). A combination of Laminarin and HC-030031 further reduced the β-glucan-induced effect. Indeed, our fiber activity results showed that the baseline fiber activity and the sensitivity of CSLV afferents were markedly elevated by β-glucan instillation, with a similar timeframe in anesthetized, artificially ventilated rats. Moreover, this effect was reduced by treatment with HC-030031. In isolated rat CSLV neurons, the β-glucan perfusion caused a similar pattern of potentiating effects on capsaicin-induced Ca2+ transients, and β-glucan-induced sensitization was abolished by Laminarin pretreatment. Furthermore, the immunofluorescence results showed that there was a co-localization of TRPV1 and Dectin-1 expression in the DiI-labeled lung vagal neurons. These results suggest that CSLV afferents play a vital role in the airway hypersensitivity elicited by airway exposure to β-glucan. The TRPA1 and Dectin-1 receptors appear to be primarily responsible for generating β-glucan-induced airway hypersensitivity.

Authors+Show Affiliations

Department of Physiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 110, Taiwan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32961891

Citation

Lin, You Shuei, et al. "Involvement of Capsaicin-Sensitive Lung Vagal Neurons and TRPA1 Receptors in Airway Hypersensitivity Induced By 1,3-β-D-Glucan in Anesthetized Rats." International Journal of Molecular Sciences, vol. 21, no. 18, 2020.
Lin YS, Huang IH, Lan SH, et al. Involvement of Capsaicin-Sensitive Lung Vagal Neurons and TRPA1 Receptors in Airway Hypersensitivity Induced by 1,3-β-D-Glucan in Anesthetized Rats. Int J Mol Sci. 2020;21(18).
Lin, Y. S., Huang, I. H., Lan, S. H., Chen, C. L., Chen, Y. Y., Chan, N. J., & Hsu, C. C. (2020). Involvement of Capsaicin-Sensitive Lung Vagal Neurons and TRPA1 Receptors in Airway Hypersensitivity Induced by 1,3-β-D-Glucan in Anesthetized Rats. International Journal of Molecular Sciences, 21(18). https://doi.org/10.3390/ijms21186845
Lin YS, et al. Involvement of Capsaicin-Sensitive Lung Vagal Neurons and TRPA1 Receptors in Airway Hypersensitivity Induced By 1,3-β-D-Glucan in Anesthetized Rats. Int J Mol Sci. 2020 Sep 18;21(18) PubMed PMID: 32961891.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Involvement of Capsaicin-Sensitive Lung Vagal Neurons and TRPA1 Receptors in Airway Hypersensitivity Induced by 1,3-β-D-Glucan in Anesthetized Rats. AU - Lin,You Shuei, AU - Huang,I-Hsuan, AU - Lan,Sheng-Hsuan, AU - Chen,Chia-Ling, AU - Chen,Yueh-Yin, AU - Chan,Nai-Ju, AU - Hsu,Chun-Chun, Y1 - 2020/09/18/ PY - 2020/08/17/received PY - 2020/09/13/revised PY - 2020/09/15/accepted PY - 2020/9/23/entrez PY - 2020/9/24/pubmed PY - 2021/3/16/medline KW - Dectin-1 KW - TRPA1 KW - afferent sensitization KW - airway hypersensitivity KW - capsaicin-sensitive lung vagal afferents KW - fungi KW - glucan KW - sensory neuron JF - International journal of molecular sciences JO - Int J Mol Sci VL - 21 IS - 18 N2 - Airway exposure to 1,3-β-D-glucan (β-glucan), an essential component of the cell wall of several pathogenic fungi, causes various adverse responses, such as pulmonary inflammation and airway hypersensitivity. The former response has been intensively investigated; however, the mechanism underlying β-glucan-induced airway hypersensitivity is unknown. Capsaicin-sensitive lung vagal (CSLV) afferents are very chemosensitive and stimulated by various insults to the lungs. Activation of CSLV afferents triggers several airway reflexes, such as cough. Furthermore, the sensitization of these afferents is known to contribute to the airway hypersensitivity during pulmonary inflammation. This study was carried out to determine whether β-glucan induces airway hypersensitivity and the role of the CSLV neurons in this hypersensitivity. Our results showed that the intratracheal instillation of β-glucan caused not only a distinctly irregular pattern in baseline breathing, but also induced a marked enhancement in the pulmonary chemoreflex responses to capsaicin in anesthetized, spontaneously breathing rats. The potentiating effect of β-glucan was found 45 min later and persisted at 90 min. However, β-glucan no longer caused the irregular baseline breathing and the potentiating of pulmonary chemoreflex responses after treatment with perineural capsaicin treatment that blocked the conduction of CSLV fibers. Besides, the potentiating effect of β-glucan on pulmonary chemoreflex responses was significantly attenuated by N-acetyl-L-cysteine (a ROS scavenger), HC-030031 (a TRPA1 antagonist), and Laminarin (a Dectin-1 antagonist). A combination of Laminarin and HC-030031 further reduced the β-glucan-induced effect. Indeed, our fiber activity results showed that the baseline fiber activity and the sensitivity of CSLV afferents were markedly elevated by β-glucan instillation, with a similar timeframe in anesthetized, artificially ventilated rats. Moreover, this effect was reduced by treatment with HC-030031. In isolated rat CSLV neurons, the β-glucan perfusion caused a similar pattern of potentiating effects on capsaicin-induced Ca2+ transients, and β-glucan-induced sensitization was abolished by Laminarin pretreatment. Furthermore, the immunofluorescence results showed that there was a co-localization of TRPV1 and Dectin-1 expression in the DiI-labeled lung vagal neurons. These results suggest that CSLV afferents play a vital role in the airway hypersensitivity elicited by airway exposure to β-glucan. The TRPA1 and Dectin-1 receptors appear to be primarily responsible for generating β-glucan-induced airway hypersensitivity. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/32961891/Involvement_of_Capsaicin_Sensitive_Lung_Vagal_Neurons_and_TRPA1_Receptors_in_Airway_Hypersensitivity_Induced_by_13_��_D_Glucan_in_Anesthetized_Rats_ L2 - https://www.mdpi.com/resolver?pii=ijms21186845 DB - PRIME DP - Unbound Medicine ER -