Polymerized Type I Collagen Reverts Airway Hyperresponsiveness and Fibrosis in a Guinea Pig Asthma Model

Bazán‐Perkins, Blanca; Campos, Marı́a G.; Sánchez-Guerrero, Edgar

doi:10.5772/25563

Cited by 4 publications

(4 citation statements)

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“…Group II exhibited less lymphocytic infiltrate possibly because the compound reduces chemotaxis and lymphocyte stimulation in chronic inflammatory processes [6], which corroborates the findings of tracheal surgery studies [10, 23] and studies performed in guinea pigs with asthma treated with Collagen-PVP, which showed low numbers of lymphocytes during tissue remodeling [25]. Our findings also corroborate those by Furuzawa-Carballeda et al [26], who assessed the safety of Collagen-PVP in vitro and in vivo and noted that this biopharmaceutical does not stimulate lymphocyte proliferation.…”

Section: Discussionsupporting

confidence: 66%

“…Animals in groups I and III developed more severe histological inflammation because the treatments applied in these groups do not exhibit anti-inflammatory activity, and our findings corroborate other studies of the use of MMC for the treatment of TS that reported that this drug causes lesion site irritation up to two months after its application, which favors inflammation [ 8 , 20 ]. Conversely, animals treated with Collagen-PVP developed mild-to-moderate inflammation because this drug exhibits anti-inflammatory properties over short and long periods of administration, as previously observed in clinical and experimental studies of patients with rheumatoid arthritis, hypertrophic skin scars, scleroderma, bedsores, and posttracheoplasty scars [ 10 , 25 , 26 ]. The animals treated with PFD showed no-to-mild inflammation because its oxidative stress-preventive properties inhibited the recruitment of proinflammatory cells [ 11 ], as observed in the present study and reported by studies of the effects of PFD on experimental models of pulmonary fibrosis [ 16 , 27 ].…”

Section: Discussionmentioning

confidence: 88%

“…Conversely, animals treated with Collagen-PVP developed mild-to-moderate inflammation because this drug exhibits anti-inflammatory properties over short and long periods of administration, as previously observed in clinical and experimental studies of patients with rheumatoid arthritis, hypertrophic skin scars, scleroderma, bedsores, and posttracheoplasty scars [10, 25, 26]. The animals treated with PFD showed no-to-mild inflammation because its oxidative stress-preventive properties inhibited the recruitment of proinflammatory cells [11], as observed in the present study and reported by studies of the effects of PFD on experimental models of pulmonary fibrosis [16, 27].…”

Section: Discussionmentioning

confidence: 92%

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Effects of Pirfenidone and Collagen-Polyvinylpyrrolidone on Macroscopic and Microscopic Changes, TGF-β1 Expression, and Collagen Deposition in an Experimental Model of Tracheal Wound Healing

Olmos-Zuñiga

Silva-Martínez

Jasso-Victoria

et al. 2017

BioMed Research International

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Tracheal stenosis (TS) is a fibrosis originated by prolonged inflammation and increased transforming growth factor beta 1 (TGF-β1) expression and collagen deposition (CD) in the tracheal wound. Several wound-healing modulators (WHMs) have been used to modulate the tracheal healing process and prevent TS, but they have failed, justifying the need to evaluate alternative WHM. The pirfenidone (PFD) and collagen-polyvinylpyrrolidone (Collagen-PVP) decrease inflammation and fibrosis. This study assessed the effect of PFD administration and Collagen-PVP topical application on macroscopic and microscopic changes, TGF-β1 expression, and CD in an experimental model of tracheal wound healing. Forty Wistar rats underwent cervical tracheoplasty, were divided into 4 groups (n = 10), and were treated with different WHM: group I, saline solution (SS); group II, Collagen-PVP; group III, mitomycin C (MMC); and group IV, 40 mg/kg PFD. Four weeks after surgery, the macroscopic and microscopic changes, in situ TGF-β1 expression, and CD in posttracheoplasty scars were evaluated. The animals treated with Collagen-PVP and PFD developed less inflammation and fibrosis than animals in the other study groups (p < 0.05, Kruskal-Wallis) and, moreover, showed lower TGF-β1 expression and CD than animals in group I (p < 0.05, ANOVA and Tukey's test). In conclusion, PFD and Collagen-PVP decrease inflammation, fibrosis, TGFβ-1 expression, and CD in the posttracheoplasty rats' scar.

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Section: Discussionsupporting

confidence: 66%

Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 92%

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Effects of Pirfenidone and Collagen-Polyvinylpyrrolidone on Macroscopic and Microscopic Changes, TGF-β1 Expression, and Collagen Deposition in an Experimental Model of Tracheal Wound Healing

Olmos-Zuñiga

Silva-Martínez

Jasso-Victoria

et al. 2017

BioMed Research International

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“…Direct stimulation of ASM with agonists such as histamine or indirect provocation with antigens in guinea pigs produce robust airway obstruction because guinea pigs have a large ASM mass [ 17 ]. In addition to the extrinsic responses induced by direct and indirect provocation, the guinea pig asthma model has shown an increase in intrinsic baseline tone [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Role of airway smooth muscle cell phenotypes in airway tone and obstruction in guinea pig asthma model

Álvarez-Santos

Álvarez-González

Eslava-De-Jesus

et al. 2022

Allergy Asthma Clin Immunol

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Background Airway obstruction (AO) in asthma is driven by airway smooth muscle (ASM) contraction. AO can be induced extrinsically by direct stimulation of ASM with contractile agonists as histamine, or by indirect provocation with antigens as ovalbumin, while the airway tone is dependent on intrinsic mechanisms. The association of the ASM phenotypes involved in different types of AO and airway tone in guinea pigs was evaluated. Methods Guinea pigs were sensitized to ovalbumin and challenged with antigen. In each challenge, the maximum OA response to ovalbumin was determined, and before the challenges, the tone of the airways. At third challenge, airway responsiveness (AR) to histamine was evaluated and ASM cells from trachea were disaggregated to determinate: (a) by flow cytometry, the percentage of cells that express transforming growth factor-β1 (TGF-β1), interleukin-13 (IL-13) and sarco-endoplasmic Ca2+ ATPase-2b (SERCA2b), (b) by RT-PCR, the SERCA2B gene expression, (c) by ELISA, reduced glutathione (GSH) and, (d) Ca2+ sarcoplasmic reticulum refilling rate by microfluorometry. Control guinea pig group received saline instead ovalbumin. Results Antigenic challenges in sensitized guinea pigs induced indirect AO, AR to histamine and increment in airway tone at third challenge. No relationship was observed between AO induced by antigen and AR to histamine with changes in airway tone. The extent of antigen-induced AO was associated with both, TGF-β1 expression in ASM and AR degree. The magnitude of AR and antigen-induced AO showed an inverse correlation with GSH levels in ASM. The airway tone showed an inverse association with SERCA2b expression. Conclusions Our data suggest that each type of AO and airway tone depends on different ASM phenotypes: direct and indirect AO seems to be sensitive to the level of oxidative stress; indirect obstruction induced by antigen appears to be influenced by the expression of TGF-β1 and the SERCA2b expression level plays a role in the airway tone.

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Different airway smooth muscle cells phenotypes are involved in intrinsic and extrinsic obstruction in guinea pig asthma model

Álvarez-Santos

Álvarez-González

Elizabeth

et al. 2020

Preprint

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Background: Airway obstruction in asthma is driven by airway smooth muscle (ASM) contraction. Airway obstruction can be induced extrinsically by direct stimulation of ASM with contractile agonists or by indirect provocation with antigens, while the airway baseline tone is dependent on intrinsic obstruction. The ASM phenotypes involved in all types of obstruction seem to be related.Methods: To determination the associations of the ASM phenotypes involved in different types of airway obstruction, guinea pigs were sensitized to ovalbumin and repetitively challenged with antigen. At the third challenge, histamine provocation was used to evaluate airway responsiveness (AR), and lung samples were obtained to calculate the airway wall area. ASM cells from the trachea were disaggregated to determine 1) the percentage of cells that expressed transforming growth factor-β1 (TGF-β1), interleukin-13 (IL-13) and sarco-endoplasmic Ca2+ ATPase-2b (SERCA2b) by flow cytometry; 2) SERCA2B gene expression by RT-PCR; 3) the level of reduced glutathione (GSH) by ELISA; and 4) the sarcoplasmic reticulum Ca2+ refilling rate by microfluorometry. The control guinea pig group received only saline instead of ovalbumin. Comparisons were made using t-tests, and the associations were determined using Spearman correlation coefficient analysis.Results: Antigenic challenges induced airway obstruction and progressive incremental changes in airway baseline tone. The AR to histamine and the expression of TGF-β1 in ASM cells was increased in the asthma model. The airway wall mass and expression of IL-13 and SERCA2b in ASM cells were similar between groups. SERCA2B gene expression and GSH levels were reduced in the asthma group. The extent of antigen-induced airway obstruction was directly associated with ASM cell TGF-β1 expression and the degree of AR. The magnitude of AR and antigen-induced airway obstruction showed an inverse correlation with GSH levels. The airway baseline tone showed an inverse association with SERCA2b expression. No relationship was observed between direct or indirect airway obstruction and the airway tone. After caffeine withdrawal, the rate of sarcoplasmic reticulum Ca2+ refilling was similar in both groups.Conclusions: Each type of airway obstruction depends on different ASM phenotypes: 1) direct and indirect airway obstruction seems to be sensitive to the level of ASM oxidative stress; 2) indirect obstruction induced by antigen appears to be influenced by the expression of TGF-β1 in ASM; and 3) the SERCA2b expression level in ASM cells plays a role in the intrinsic airway tone.

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Polymerized Type I Collagen Reverts Airway Hyperresponsiveness and Fibrosis in a Guinea Pig Asthma Model

Abstract: Asthma is a chronic, heterogeneous and variable disease in which airways inflammation, transient obstruction and hyperresponsiveness are the major features of the illness (

Cited by 4 publications

References 44 publications

Effects of Pirfenidone and Collagen-Polyvinylpyrrolidone on Macroscopic and Microscopic Changes, TGF-β1 Expression, and Collagen Deposition in an Experimental Model of Tracheal Wound Healing

Effects of Pirfenidone and Collagen-Polyvinylpyrrolidone on Macroscopic and Microscopic Changes, TGF-β1 Expression, and Collagen Deposition in an Experimental Model of Tracheal Wound Healing

Role of airway smooth muscle cell phenotypes in airway tone and obstruction in guinea pig asthma model

Different airway smooth muscle cells phenotypes are involved in intrinsic and extrinsic obstruction in guinea pig asthma model

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