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Interstitial collagen turnover during airway remodeling in acute and chronic experimental asthma

View Article: PubMed Central - PubMed

ABSTRACT

Asthma airway remodeling is characterized by the thickening of the basement membrane (BM) due to an increase in extracellular matrix (ECM) deposition, which contributes to the irreversibility of airflow obstruction. Interstitial collagens are the primary ECM components to be increased during the fibrotic process. The aim of the present study was to examine the interstitial collagen turnover during the course of acute and chronic asthma, and 1 month after the last exposure to the allergen. Guinea pigs sensitized to ovalbumin (OVA) and exposed to 3 further OVA challenges (acute model) or 12 OVA challenges (chronic model) were used as asthma experimental models. A group of animals from either model was sacrificed 1 h or 1 month after the last OVA challenge. Collagen distribution, collagen content, interstitial collagenase activity and matrix metalloproteinase (MMP)-1, MMP-13 and tissue inhibitor of metalloproteinase (TIMP)-1 protein expression levels were measured in the lung tissue samples from both experimental models. The results revealed that collagen deposit in bronchiole BM, adventitial and airway smooth muscle layers was increased in both experimental models as well as lung tissue collagen concentration. These structural changes persisted 1 month after the last OVA challenge. In the acute model, a decrease in collagenase activity and in MMP-1 concentration was observed. Collagenase activity returned to basal levels, and an increase in MMP-1 and MMP-13 expression levels along with a decrease in TIMP-1 expression levels were observed in animals sacrificed 1 month after the last OVA challenge. In the chronic model, there were no changes in collagenase activity or in MMP-13 concentration, although MMP-1 expression levels increased. One month later, an increase in collagenase activity was observed, although MMP-1 and TIMP-1 levels were not altered. The results of the present study suggest that even when the allergen challenges were discontinued, and collagenase activity and MMP-1 expression increased, fibrosis remained, contributing to the irreversibility of bronchoconstriction.

No MeSH data available.


Related in: MedlinePlus

Airway bronchoconstriction induced by OVA challenges in sensitized guinea pigs. Bronchoconstriction induced by OVA challenges in sensitized guinea pigs was recorded and an average of maximum airway resistance Rmax (acute model white circles and chronic model white squares) was obtained. Control animals were challenged with physiological saline solution (acute model black circles and chronic model black squares). Significant differences were observed between the experimental and control groups. #P<0.01 and *P<0.01, vs, the respective control group. Symbols represent means ± standard error. Penh, airway obstruction index; OVA, ovalbumin.
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f2-etm-0-0-3509: Airway bronchoconstriction induced by OVA challenges in sensitized guinea pigs. Bronchoconstriction induced by OVA challenges in sensitized guinea pigs was recorded and an average of maximum airway resistance Rmax (acute model white circles and chronic model white squares) was obtained. Control animals were challenged with physiological saline solution (acute model black circles and chronic model black squares). Significant differences were observed between the experimental and control groups. #P<0.01 and *P<0.01, vs, the respective control group. Symbols represent means ± standard error. Penh, airway obstruction index; OVA, ovalbumin.

Mentions: Basal Penh values and initial histamine curve PD200 values were similar in animals from the control and both asthma model groups (data not shown). Saline nebulization did not modify Penh basal values in control animals. OVA challenges in sensitized animals generated a reversible bronchoconstriction, defined by a transient Penh increment, which lasted ~2 h. This percentage increase in Penh values in the experimental models (440.9±33.9% in the 35 days group and 400±30.8% in the 125 days group) was significantly higher, as compared with Penh values in the control groups (112.9±2.9% and 130.2±6.7% in the 35 and 125 days control groups respectively; P<0.01; Fig. 2).


Interstitial collagen turnover during airway remodeling in acute and chronic experimental asthma
Airway bronchoconstriction induced by OVA challenges in sensitized guinea pigs. Bronchoconstriction induced by OVA challenges in sensitized guinea pigs was recorded and an average of maximum airway resistance Rmax (acute model white circles and chronic model white squares) was obtained. Control animals were challenged with physiological saline solution (acute model black circles and chronic model black squares). Significant differences were observed between the experimental and control groups. #P<0.01 and *P<0.01, vs, the respective control group. Symbols represent means ± standard error. Penh, airway obstruction index; OVA, ovalbumin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4998200&req=5

f2-etm-0-0-3509: Airway bronchoconstriction induced by OVA challenges in sensitized guinea pigs. Bronchoconstriction induced by OVA challenges in sensitized guinea pigs was recorded and an average of maximum airway resistance Rmax (acute model white circles and chronic model white squares) was obtained. Control animals were challenged with physiological saline solution (acute model black circles and chronic model black squares). Significant differences were observed between the experimental and control groups. #P<0.01 and *P<0.01, vs, the respective control group. Symbols represent means ± standard error. Penh, airway obstruction index; OVA, ovalbumin.
Mentions: Basal Penh values and initial histamine curve PD200 values were similar in animals from the control and both asthma model groups (data not shown). Saline nebulization did not modify Penh basal values in control animals. OVA challenges in sensitized animals generated a reversible bronchoconstriction, defined by a transient Penh increment, which lasted ~2 h. This percentage increase in Penh values in the experimental models (440.9±33.9% in the 35 days group and 400±30.8% in the 125 days group) was significantly higher, as compared with Penh values in the control groups (112.9±2.9% and 130.2±6.7% in the 35 and 125 days control groups respectively; P<0.01; Fig. 2).

View Article: PubMed Central - PubMed

ABSTRACT

Asthma airway remodeling is characterized by the thickening of the basement membrane (BM) due to an increase in extracellular matrix (ECM) deposition, which contributes to the irreversibility of airflow obstruction. Interstitial collagens are the primary ECM components to be increased during the fibrotic process. The aim of the present study was to examine the interstitial collagen turnover during the course of acute and chronic asthma, and 1 month after the last exposure to the allergen. Guinea pigs sensitized to ovalbumin (OVA) and exposed to 3 further OVA challenges (acute model) or 12 OVA challenges (chronic model) were used as asthma experimental models. A group of animals from either model was sacrificed 1 h or 1 month after the last OVA challenge. Collagen distribution, collagen content, interstitial collagenase activity and matrix metalloproteinase (MMP)-1, MMP-13 and tissue inhibitor of metalloproteinase (TIMP)-1 protein expression levels were measured in the lung tissue samples from both experimental models. The results revealed that collagen deposit in bronchiole BM, adventitial and airway smooth muscle layers was increased in both experimental models as well as lung tissue collagen concentration. These structural changes persisted 1 month after the last OVA challenge. In the acute model, a decrease in collagenase activity and in MMP-1 concentration was observed. Collagenase activity returned to basal levels, and an increase in MMP-1 and MMP-13 expression levels along with a decrease in TIMP-1 expression levels were observed in animals sacrificed 1 month after the last OVA challenge. In the chronic model, there were no changes in collagenase activity or in MMP-13 concentration, although MMP-1 expression levels increased. One month later, an increase in collagenase activity was observed, although MMP-1 and TIMP-1 levels were not altered. The results of the present study suggest that even when the allergen challenges were discontinued, and collagenase activity and MMP-1 expression increased, fibrosis remained, contributing to the irreversibility of bronchoconstriction.

No MeSH data available.


Related in: MedlinePlus