Effect of lipopolysaccharide on the responsiveness of equine bronchial tissue

Calzetta, Luigino; Rogliani, Paola; Pistocchini, Elena; Mattei, Maurizio; Cito, Giuseppe; Alfonsi, Pietro; Page, Clive; Matera, Maria Gabriella

doi:10.1016/j.pupt.2018.01.010

Cited by 8 publications

(7 citation statements)

References 52 publications

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“…The present study demonstrated that TRPV1 was present as mRNA and protein in the equine synovial membrane in healthy and diseased joints. These results are consistent with previous studies, where TRPV1 has been found in synovial tissue from several other species [26][27][28], and in both neural and respiratory tissue in the horse [45].…”

Section: Discussionsupporting

confidence: 94%

Identification and Quantification of Transient Receptor Potential Vanilloid 1 (TRPV1) in Equine Articular Tissue

Braucke

Frederiksen

Berg

et al. 2020

Animals

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Joint pain and osteoarthritis (OA) are some of the most common causes of lameness in horses, and most of the available treatments focus on symptomatic relief without a disease-modifying effect. TRPV1 is a potential target for treating joint diseases, including OA, and the present study aims to investigate if the TRPV1 receptor is present in equine articular tissue and determine whether the number of receptors is upregulated in joint inflammation. Metacarpo/metatarsophalangeal (MCP/MTP) joints from 15 horses euthanised for reasons unrelated to this study were included. Based on synovial fluid analysis, macroscopic evaluation, and magnetic resonance imaging (MRI), joints were divided into two groups: healthy joints and joints with pathology. ELISA analysis was performed on synovial tissue harvested from all joints. TPRV1 was found in all joints. The mean concentration of TRPV1 compared to total protein in healthy joints (8.4 × 10 −7 ng/mL) and joints with pathology (12.9 × 10 −7 ng/mL) differed significantly (p = 0.01, t-test with Welch correction). Quantitative real-time reverse transcriptase PCR analysis was performed on RNA isolates from synovial tissue from all joints. TRPV1 mRNA expression ratio normalized to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in healthy joints (0.16 (SD: 0.19)) and joints with pathology (0.24 (SD: 0.14)) did not differ significantly (p = 0.43, t-test with Welch correction). mRNA expression of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) was very low for both groups. In conclusion, TRPV1 was detected both on mRNA and the protein level, with a higher expression of TRPV1 in samples from joints with pathology. Future studies will determine the clinical potential of equine TRPV1 as a target in the management of joint pain and inflammation.Animals 2020, 10, 506 2 of 15 described aetiology is trauma-either as a single event or as a series of microtrauma. This will induce an inflammatory response, which, in turn, will drive the process of articular cartilage breakdown and remodelling of the surrounding bone [4]. Consequently, horses diagnosed with OA are often retired or euthanised.There is a broad spectrum of treatments for equine OA. Most of them are anti-inflammatory and pain-relieving without a true disease-modifying effect, although regenerative medicine in regard to equine OA is a rapidly evolving area [5][6][7][8]. Two of the drug groups most commonly used for treating the symptoms related to equine OA are nonsteroidal anti-inflammatory drugs (NSAIDs) and intra-articular corticosteroids, often in combination. NSAIDs are predisposing for gastrointestinal ulceration and are potentially nephrotoxic, and corticosteroids are potentially chondrotoxic [9][10][11][12]. In human medicine, so-called disease-modifying osteoarthritis drugs (DMOADs) are being investigated in an attempt to stop the disease progression, as well as being pain-relieving and anti-inflammatory. However, an effective disease-modifying drug has not yet been developed [13].Several authors point to the ...

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Section: Discussionsupporting

confidence: 94%

Identification and Quantification of Transient Receptor Potential Vanilloid 1 (TRPV1) in Equine Articular Tissue

Braucke

Frederiksen

Berg

et al. 2020

Animals

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“…The ex vivo study by Calzetta et al, 2018 confirms and extends the previous results by Venugopal et al, 2009 and suggests that the environmental exposure to bacterial of lipopolysaccharides may represent a crucial factor in modulating the bronchial responsiveness of severe equine asthma [ 20 , 23 ]. A chronic exposure to high concentration of inhaled endotoxin in fact has a deleterious effect in equine distal airways: it triggers dysfunctional airway smooth muscle (ASM) contractility due to the stimulation of capsaicin-sensitive sensory nerves, increased the release of NKA and the activation of NK2 receptors.…”

Section: Discussionsupporting

confidence: 68%

“…However, little information exists regarding the involvement of NKA receptors in the horse, moreover limited to the intestine [ 50 ] and to the lung of horses affected by EA [ 20 ]. Recently, the receptors of the capsaicin sensitive-sensory nerves stimulated by bacterial of lipopolysaccharides, capable of inducing neurogenic inflammation [ 23 ] as occur in human airways [ 48 ] have been investigated in equine bronchial tissue.…”

Section: Discussionmentioning

confidence: 99%

“…A tachykinin mediator with a physiological and pathological role in respiratory function is a neuropeptide called neurokinin A (NKA), which is involved in the processes of bronchoconstriction and neurogenic inflammation in asthmatic patients, with potential therapeutic implications using selective NKA receptor antagonists [ 20 ]. To the best of our knowledge, only two studies investigated the role of neurokinin-A (NKA) in the horse respiratory tract [ 20 , 23 ], and only one by immunohistochemical methods [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

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Immunohistochemical Expression of Neurokinin-A and Interleukin-8 in the Bronchial Epithelium of Horses with Severe Equine Asthma Syndrome during Asymptomatic, Exacerbation, and Remission Phase

Morini

Peli

Rinnovati

et al. 2021

Animals

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Severe equine asthma (EA) syndrome is a chronic obstructive disease characterized by exaggerated contraction, inflammation, and structural alteration of the airways in adult horses, when exposed to airborne molds and particulate material. However, little is known about the relationship between the degree and type of inflammation on one hand, and the severity of the disease and the response to treatment on the other. Furthermore, to date, very few studies evaluate the diagnostic value of histology and immunohistochemical features of endoscopic biopsies on subjects with severe equine asthma. To investigate the expression of two inflammatory markers (NKA and IL-8) before, during, and after the exacerbation of severe EA, a histological and immunohistochemical study was carried out on a series of biopsy samples collected by bronchoscopy from six EA-affected horses subjected to process exacerbation through environmental stimuli and then to pharmacological treatment. The application of a histological biopsy scoring system revealed a significant difference between control cases and the EA-affected horses in all experimental phases (asymptomatic, early exacerbation phase, late exacerbation phase, and remission phase). For immunohistochemistry (IHC), only the intensity of NKA positivity increases significantly between control horses and the EA horses at late exacerbation and remission phases. In EA-affected horses, a difference was detected by comparing histology between asymptomatic and remission phase, meanwhile, NKA and IL-8 showed no differences between the experimental phases. Based on these results we can assert that: (1) The endoscopic biopsies generate reliable and homogeneous samples in the entire bronchial tree; (2) the clinical improvement associated with treatment is characterized by a significant worsening of the histological findings; and (3) the NKA immunopositivity seems to increase significantly rather than decrease, as one would have expected, after pharmacological treatment. Further studies are necessary both to implement the number of samples and to use other markers of inflammation to characterize the potential role of cytokines in the diagnosis and therapeutic approach of severe equine asthma.

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“…A change in R L ≥1 cm H 2 O/L/s may also help clinicians to identify whether individual asthmatic horses could be clinically responsive to a long‐acting β 2 ‐agonist (LABA) instead of a long‐acting muscarinic antagonist (LAMA), and vice versa, when the agents are administered in monotherapy as rescue medication in subjects with acute airway hyper responsiveness, or whether adding a second bronchodilator agent may clinically improve lung function . The MID based on change in R L might guide the choice of maintenance therapy .…”

Section: Discussionmentioning

confidence: 99%

Clinical efficacy of bronchodilators in equine asthma: Looking for minimal important difference

Calzetta

Crupi

Roncada

et al. 2019

Equine Veterinary Journal

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Summary Background Airway obstruction is the main trait of severe equine asthma that affects respiratory function and elicits detrimental effects on clinical presentation. Only few and underpowered clinical studies have investigated the impact of improvement in lung function induced by bronchodilators on the clinical signs of asthma‐affected horses. Objectives To identify the minimal important difference (MID) in lung function elicited by bronchodilator leading to a meaningful improvement in clinical signs. Study design Pairwise meta‐analysis and meta‐regression analysis. Methods Literature searches were performed for studies that investigated the effect of bronchodilator therapy on lung function and clinical condition of asthmatic horses. The relationship between the change in lung function variables and clinical score was analysed via random‐effect meta‐regression. One‐point change of the Improved clinically Detectable Equine Asthma Scoring System (IDEASS) score was used to identify the MID. Results A significant (P<0.05) relationship was found between the changes in IDEASS score and maximum change in transpulmonary pressure (ΔPplmax) or pulmonary resistance (RL). Since only the model resulting for RL passed through the origin (Y‐intercept when X = 0: −0.31, 95% CI −0.75 to 0.14), this variable was used to identify the MID correlated with a meaningful improvement in clinical signs. The resulting MID value was a change in RL of 0.63 cm H2O/L/s (95% CI 0.33–0.94), representing the slope of meta‐regression model (high quality of evidence). Main limitations No long‐term studies investigated the effect of bronchodilator agents on both lung function and clinical signs in asthmatic horses. Conclusions In conclusion, bronchodilator pharmacotherapy in equine asthma elicits clinically meaningful effect when RL increases ≥1 cm H2O/L/s, a value indicating the MID. Assessing the MID based on change in RL may improve the quality of evidence and the scientific impact of future clinical trials as it extends beyond the simple, and limiting, evaluation of statistical significance.

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Effect of lipopolysaccharide on the responsiveness of equine bronchial tissue

Cited by 8 publications

References 52 publications

Identification and Quantification of Transient Receptor Potential Vanilloid 1 (TRPV1) in Equine Articular Tissue

Identification and Quantification of Transient Receptor Potential Vanilloid 1 (TRPV1) in Equine Articular Tissue

Immunohistochemical Expression of Neurokinin-A and Interleukin-8 in the Bronchial Epithelium of Horses with Severe Equine Asthma Syndrome during Asymptomatic, Exacerbation, and Remission Phase

Clinical efficacy of bronchodilators in equine asthma: Looking for minimal important difference

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