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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 hyperresponsiveness to histamine induced by OVA challenge in sensitized guinea pigs. Guinea pigs in both experimental models and their respective controls were administered increasing doses of nebulized histamine prior to OVA (sensitized) or saline solution (control) administration. Once the OVA-induced bronchoconstriction subsided, a second histamine dose-response curve was built. Responses to histamine are expressed as provocative dose ratio. Histamine PD200 ratio was significantly decreased in both asthma models compared with their respective control groups. The discontinuous line delimited the border between hyperresponsiveness (below the line) and hyporresponsiveness (above the line). **P=0.01 and *P=0.04, vs. the respective control group. Bars represent means ± standard error. OVA, ovalbumin; PD200, provocative dose 200%.
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f3-etm-0-0-3509: Airway hyperresponsiveness to histamine induced by OVA challenge in sensitized guinea pigs. Guinea pigs in both experimental models and their respective controls were administered increasing doses of nebulized histamine prior to OVA (sensitized) or saline solution (control) administration. Once the OVA-induced bronchoconstriction subsided, a second histamine dose-response curve was built. Responses to histamine are expressed as provocative dose ratio. Histamine PD200 ratio was significantly decreased in both asthma models compared with their respective control groups. The discontinuous line delimited the border between hyperresponsiveness (below the line) and hyporresponsiveness (above the line). **P=0.01 and *P=0.04, vs. the respective control group. Bars represent means ± standard error. OVA, ovalbumin; PD200, provocative dose 200%.

Mentions: When hyperresponsiveness to histamine was evaluated, no changes in PD200 values were observed in the saline-challenged control animals. Guinea pigs from both asthma models exhibited a significant decrease in histamine PD200 ratio as compared with the control group (0.84±0.1 mg/ml and 0.47±0.06 mg/ml for the control and 35 day asthma model group, respectively; P=0.01; and 1.23±0.21 mg/ml and 0.65±0.06 mg/ml for the control and 125 day asthma model group, respectively; P=0.04; Fig. 3).


Interstitial collagen turnover during airway remodeling in acute and chronic experimental asthma
Airway hyperresponsiveness to histamine induced by OVA challenge in sensitized guinea pigs. Guinea pigs in both experimental models and their respective controls were administered increasing doses of nebulized histamine prior to OVA (sensitized) or saline solution (control) administration. Once the OVA-induced bronchoconstriction subsided, a second histamine dose-response curve was built. Responses to histamine are expressed as provocative dose ratio. Histamine PD200 ratio was significantly decreased in both asthma models compared with their respective control groups. The discontinuous line delimited the border between hyperresponsiveness (below the line) and hyporresponsiveness (above the line). **P=0.01 and *P=0.04, vs. the respective control group. Bars represent means ± standard error. OVA, ovalbumin; PD200, provocative dose 200%.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3-etm-0-0-3509: Airway hyperresponsiveness to histamine induced by OVA challenge in sensitized guinea pigs. Guinea pigs in both experimental models and their respective controls were administered increasing doses of nebulized histamine prior to OVA (sensitized) or saline solution (control) administration. Once the OVA-induced bronchoconstriction subsided, a second histamine dose-response curve was built. Responses to histamine are expressed as provocative dose ratio. Histamine PD200 ratio was significantly decreased in both asthma models compared with their respective control groups. The discontinuous line delimited the border between hyperresponsiveness (below the line) and hyporresponsiveness (above the line). **P=0.01 and *P=0.04, vs. the respective control group. Bars represent means ± standard error. OVA, ovalbumin; PD200, provocative dose 200%.
Mentions: When hyperresponsiveness to histamine was evaluated, no changes in PD200 values were observed in the saline-challenged control animals. Guinea pigs from both asthma models exhibited a significant decrease in histamine PD200 ratio as compared with the control group (0.84±0.1 mg/ml and 0.47±0.06 mg/ml for the control and 35 day asthma model group, respectively; P=0.01; and 1.23±0.21 mg/ml and 0.65±0.06 mg/ml for the control and 125 day asthma model group, respectively; P=0.04; Fig. 3).

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