Background: Airway inflammation and airway hyperresponsiveness (AHR) are pivotal characteristics of equine asthma. Lipopolysaccharide (LPS) may have a central role in modulating airway inflammation and dysfunction. Therefore, the aim of this study was to match the inflammatory and contractile profile in LPS-challenged equine isolated bronchi to identify molecular targets potentially suitable to counteract AHR in asthmatic horses. Methods: Equine isolated bronchi were incubated overnight with LPS (0.1-100 ng/ml). The contractile response to electrical field stimulation (EFS) and the levels of cytokines, chemokines, and neurokinin A (NKA) were quantified. The role of capsaicin sensitive-sensory nerves, neurokinin-2 (NK2) receptor, transient receptor potential vanilloid type 1 receptors (TRPV1), and epithelium were also investigated. Results: LPS 1 ng/ml elicited AHR to EFS (+238.17 ± 25.20% P < 0.001 vs. control). LPS significantly (P < 0.05 vs. control) increased the levels of IL-4 (+36.08 ± 1.62%), IL-5 (+38.60 ± 3.58%), IL-6 (+33.79 ± 2.59%), IL-13 (+40.91 ± 1.93%), IL-1β (+1650.16 ± 71.16%), IL-33 (+88.14 ± 8.93%), TGF-β (22.29 ± 1.03%), TNF-α (+56.13 ± 4.61%), CXCL-8 (+98.49 ± 17.70%), EOTAXIN (+32.26 ± 2.27%), MCP-1 (+49.63 ± 4.59%), RANTES (+36.38 ± 2.24%), and NKA (+112.81 ± 6.42%). Capsaicin sensitive-sensory nerves, NK2 receptor, and TRPV1 were generally involved in the LPS-mediated inflammation. Epithelium removal modulated the release of IL-1β, IL-33, and TGF-β. Only the levels of IL-6 fitted with AHR to a wide range of EFS frequencies, an effect significantly (P < 0.05) inhibited by anti-IL-6 antibody; exogenous IL-6 induced significant (P < 0.05) AHR to EFS similar to that elicited by LPS. Conclusion: Targeting IL-6 with specific antibody may represent an effective strategy to treat equine asthma, especially in those animals suffering from severe forms of this disease.

Calzetta, L., Pistocchini, E., Cito, G., Ritondo, B.l., Verri, S., Rogliani, P. (2022). Inflammatory and contractile profile in LPS-challenged equine isolated bronchi: evidence for IL-6 as a potential target against AHR in equine asthma. PULMONARY PHARMACOLOGY & THERAPEUTICS, 73-74 [10.1016/j.pupt.2022.102125].

Inflammatory and contractile profile in LPS-challenged equine isolated bronchi: evidence for IL-6 as a potential target against AHR in equine asthma

Calzetta, Luigino;Rogliani, Paola
2022-06-01

Abstract

Background: Airway inflammation and airway hyperresponsiveness (AHR) are pivotal characteristics of equine asthma. Lipopolysaccharide (LPS) may have a central role in modulating airway inflammation and dysfunction. Therefore, the aim of this study was to match the inflammatory and contractile profile in LPS-challenged equine isolated bronchi to identify molecular targets potentially suitable to counteract AHR in asthmatic horses. Methods: Equine isolated bronchi were incubated overnight with LPS (0.1-100 ng/ml). The contractile response to electrical field stimulation (EFS) and the levels of cytokines, chemokines, and neurokinin A (NKA) were quantified. The role of capsaicin sensitive-sensory nerves, neurokinin-2 (NK2) receptor, transient receptor potential vanilloid type 1 receptors (TRPV1), and epithelium were also investigated. Results: LPS 1 ng/ml elicited AHR to EFS (+238.17 ± 25.20% P < 0.001 vs. control). LPS significantly (P < 0.05 vs. control) increased the levels of IL-4 (+36.08 ± 1.62%), IL-5 (+38.60 ± 3.58%), IL-6 (+33.79 ± 2.59%), IL-13 (+40.91 ± 1.93%), IL-1β (+1650.16 ± 71.16%), IL-33 (+88.14 ± 8.93%), TGF-β (22.29 ± 1.03%), TNF-α (+56.13 ± 4.61%), CXCL-8 (+98.49 ± 17.70%), EOTAXIN (+32.26 ± 2.27%), MCP-1 (+49.63 ± 4.59%), RANTES (+36.38 ± 2.24%), and NKA (+112.81 ± 6.42%). Capsaicin sensitive-sensory nerves, NK2 receptor, and TRPV1 were generally involved in the LPS-mediated inflammation. Epithelium removal modulated the release of IL-1β, IL-33, and TGF-β. Only the levels of IL-6 fitted with AHR to a wide range of EFS frequencies, an effect significantly (P < 0.05) inhibited by anti-IL-6 antibody; exogenous IL-6 induced significant (P < 0.05) AHR to EFS similar to that elicited by LPS. Conclusion: Targeting IL-6 with specific antibody may represent an effective strategy to treat equine asthma, especially in those animals suffering from severe forms of this disease.
giu-2022
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/10 - MALATTIE DELL'APPARATO RESPIRATORIO
English
Con Impact Factor ISI
AHR
Asthma
Bronchial epithelium
Chemokines
Cytokines
Equine
IL-6
LPS
NKA
Calzetta, L., Pistocchini, E., Cito, G., Ritondo, B.l., Verri, S., Rogliani, P. (2022). Inflammatory and contractile profile in LPS-challenged equine isolated bronchi: evidence for IL-6 as a potential target against AHR in equine asthma. PULMONARY PHARMACOLOGY & THERAPEUTICS, 73-74 [10.1016/j.pupt.2022.102125].
Calzetta, L; Pistocchini, E; Cito, G; Ritondo, Bl; Verri, S; Rogliani, P
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/331303
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