Targeting the adenosinergic signaling pathway in the inflammatory response in rat lung tissue during moderate and severe chronic hypoxia

Özge Göktepe; Kemal Erdem Başaran; Pınar Alişan Suna; Demet Bolat; Arzu Yay

Makale detayları

Targeting the adenosinergic signaling pathway in the inflammatory response in rat lung tissue during moderate and severe chronic hypoxia

Yazarlar:

Özge Göktepe | Kemal Erdem Başaran | Pınar Alişan Suna | Demet Bolat | Arzu Yay

Yayıncı:

Cukurova University

Ana Başlıklar:

Göğüs Hastalıkları

Dergi:

Cukurova Medical Journal Vol.50 Issue 1, pp.22-37

Belge Tipi:

Makale

Yayın Tarihi:

3/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001343845

pISSN:

2602-3032

Anahtar kelimeler:

Özet:

 Purpose: Hypoxia occurs after inflammatory diseases in tissues and is associated with the induction of proinflammatory responses in addition to the breakdown of barriers. Adenosine receptors are critical in the initiation and regulation of this response. The effectiveness of externally applied adenosine receptor agonistsantagonists in such inflammatory diseases is noteworthy. In this study, we aimed to investigate the relationship between hypoxia, adenosine and inflammation, as well as the role of adenosine agonists and antagonists in this situation. Materials and Methods: For this purpose, two different hypoxia models, moderate and severe, were used. Using a total of 80 male Sprague-Dawley rats for both models, 4 subgroups were designed: control CON, dimethyl sulfoxide DMSO, adenosine agonist AGO; CGS-21680 and adenosine antagonist ANT; MSX-3. Rats were exposed to moderate groups 13 O2 and severe groups 10 O2 in fine-tuned normobaric hypoxia chambers for 7 days. At the end of the 7th day, ventilation measurements were made and the hypoxia model was confirmed. A2AR, CD11c, COX2, NFKB and VEGF antibody expressions were evaluated by immunofluorescence staining method by taking frozen sections from the lung tissues after the experimental stages. Results: This study showed that the expression of inflammation markers increased in experimental hypoxia models. According to the findings, while the levels of A2AR and VEGF were higher in the agonist group compared to the other groups in both models, the levels of inflammatory markers CD11c, NFKB and COX2 were significantly lower. Conclusion: Various natural and synthetic drugs are available as treating the inflammation which can be helpful in treating lung disorders. Researchers are still searching for new anti-inflammatory drugs which can produced faster response. These findings highlight the potential benefit of A2A agonists, which can be used in hypoxia-induced lung inflammation.

 Purpose: Hypoxia occurs after inflammatory diseases in tissues and is associated with the induction of proinflammatory responses in addition to the breakdown of barriers. Adenosine receptors are critical in the initiation and regulation of this response. The effectiveness of externally applied adenosine receptor agonistsantagonists in such inflammatory diseases is noteworthy. In this study, we aimed to investigate the relationship between hypoxia, adenosine and inflammation, as well as the role of adenosine agonists and antagonists in this situation. Materials and Methods: For this purpose, two different hypoxia models, moderate and severe, were used. Using a total of 80 male Sprague-Dawley rats for both models, 4 subgroups were designed: control CON, dimethyl sulfoxide DMSO, adenosine agonist AGO; CGS-21680 and adenosine antagonist ANT; MSX-3. Rats were exposed to moderate groups 13 O2 and severe groups 10 O2 in fine-tuned normobaric hypoxia chambers for 7 days. At the end of the 7th day, ventilation measurements were made and the hypoxia model was confirmed. A2AR, CD11c, COX2, NFKB and VEGF antibody expressions were evaluated by immunofluorescence staining method by taking frozen sections from the lung tissues after the experimental stages. Results: This study showed that the expression of inflammation markers increased in experimental hypoxia models. According to the findings, while the levels of A2AR and VEGF were higher in the agonist group compared to the other groups in both models, the levels of inflammatory markers CD11c, NFKB and COX2 were significantly lower. Conclusion: Various natural and synthetic drugs are available as treating the inflammation which can be helpful in treating lung disorders. Researchers are still searching for new anti-inflammatory drugs which can produced faster response. These findings highlight the potential benefit of A2A agonists, which can be used in hypoxia-induced lung inflammation.

 Purpose: Hypoxia occurs after inflammatory diseases in tissues and is associated with the induction of proinflammatory responses in addition to the breakdown of barriers. Adenosine receptors are critical in the initiation and regulation of this response. The effectiveness of externally applied adenosine receptor agonistsantagonists in such inflammatory diseases is noteworthy. In this study, we aimed to investigate the relationship between hypoxia, adenosine and inflammation, as well as the role of adenosine agonists and antagonists in this situation. Materials and Methods: For this purpose, two different hypoxia models, moderate and severe, were used. Using a total of 80 male Sprague-Dawley rats for both models, 4 subgroups were designed: control CON, dimethyl sulfoxide DMSO, adenosine agonist AGO; CGS-21680 and adenosine antagonist ANT; MSX-3. Rats were exposed to moderate groups 13 O2 and severe groups 10 O2 in fine-tuned normobaric hypoxia chambers for 7 days. At the end of the 7th day, ventilation measurements were made and the hypoxia model was confirmed. A2AR, CD11c, COX2, NFKB and VEGF antibody expressions were evaluated by immunofluorescence staining method by taking frozen sections from the lung tissues after the experimental stages. Results: This study showed that the expression of inflammation markers increased in experimental hypoxia models. According to the findings, while the levels of A2AR and VEGF were higher in the agonist group compared to the other groups in both models, the levels of inflammatory markers CD11c, NFKB and COX2 were significantly lower. Conclusion: Various natural and synthetic drugs are available as treating the inflammation which can be helpful in treating lung disorders. Researchers are still searching for new anti-inflammatory drugs which can produced faster response. These findings highlight the potential benefit of A2A agonists, which can be used in hypoxia-induced lung inflammation.

 Amaç: Hipoksi, dokulardaki inflamatuar hastalıklardan sonra ortaya çıkar ve proinflamatuar yanıtların indüklenmesiyle ilişkilidir. Adenozin reseptörleri bu yanıtın başlatılması ve düzenlenmesinde kritik öneme sahiptir. Bu tür inflamatuar hastalıklarda haricen uygulanan adenozin reseptör agonistlerininantagonistlerinin etkinliği dikkat çekicidir. Bu çalışmada hipoksi, adenozin ve inflamasyon arasındaki ilişkinin yanı sıra adenozin agonist ve antagonistlerinin bu süreçteki rolünü araştırmayı amaçladık. Gereç ve Yöntem: Bu amaçla, orta ve şiddetli olmak üzere iki farklı hipoksi modeli kullanıldı. Her iki model için toplam 80 erkek Sprague-Dawley sıçanı kullanılarak 4 alt grup tasarlandı: kontrol CON, dimetil sülfoksit DMSO, agonist AGO; CGS-21680 ve antagonist ANT; MSX-3. Sıçanlar 7 gün boyunca ince ayarlı normobarik hipoksi odalarında orta gruplarda 13 O2 ve ağır gruplarda 10 O2ye maruz bırakıldı. 7. günün sonunda ventilasyon ölçümleri yapıldı ve hipoksi modeli doğrulandı. Deneysel aşamalardan sonra akciğer dokularından dondurulmuş kesitler alınarak immünofloresan boyama yöntemi ile A2AR, CD11c, COX2, NFKB ve VEGF antikor ekspresyonları değerlendirildi. Bulgular: Bu çalışma, deneysel hipoksi modellerinde inflamatuar belirteçlerin ekspresyonunun arttığını gösterdi. Bulgulara göre, her iki modelde de agonist grubunda A2AR ve VEGF düzeyleri diğer gruplara göre daha yüksek iken, inflamasyon belirteçleri CD11c, NFKB ve COX2 düzeyleri anlamlı derecede düşüktü. Sonuç: Enflamasyonu tedavi etmek için akciğer bozukluklarının tedavisinde yardımcı olabilecek çeşitli doğal ve sentetik ilaçlar mevcuttur. Araştırmacılar hala daha hızlı yanıt verebilecek yeni antiinflamatuar ilaçları araştırıyorlar. Bu bulgular hipoksi kaynaklı akciğer inflamasyonunda kullanılabilecek A2A agonistlerinin potansiyel faydasını vurgulamaktadır.

Makale detayları

Targeting the adenosinergic signaling pathway in the inflammatory response in rat lung tissue during moderate and severe chronic hypoxia

Yazarlar:

Özge Göktepe | Kemal Erdem Başaran | Pınar Alişan Suna | Demet Bolat | Arzu Yay

Yayıncı:

Cukurova University

Ana Başlıklar:

Göğüs Hastalıkları

Dergi:

Cukurova Medical Journal Vol.50 Issue 1, pp.22-37

Belge Tipi:

Makale

Yayın Tarihi:

3/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001343845

pISSN:

2602-3032

Hypoxia

Adenosine

Adenosine agonist/antagonist

Lung toxicityHipoksi

adenozin

adenozin agonist/antagonist

akciğer toksisitesi

Sayı

Makale detayları

Yazarlar: Özge Göktepe | Kemal Erdem Başaran | Pınar Alişan Suna | Demet Bolat | Arzu Yay

Yayıncı: Cukurova University

Ana Başlıklar: Göğüs Hastalıkları

Dergi: Cukurova Medical Journal Vol.50 Issue 1, pp.22-37

Belge Tipi: Makale

Yayın Tarihi: 3/2025

Belge Dili: İngilizce

Document ID (Org No.): 2001343845

pISSN: 2602-3032

Sayı

Yazarlar:

Özge Göktepe | Kemal Erdem Başaran | Pınar Alişan Suna | Demet Bolat | Arzu Yay

Yayıncı:

Cukurova University

Ana Başlıklar:

Göğüs Hastalıkları

Dergi:

Cukurova Medical Journal Vol.50 Issue 1, pp.22-37

Belge Tipi:

Makale

Yayın Tarihi:

3/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001343845

pISSN:

2602-3032