TLR4/NF-KB SIGNALING PATHWAY IS A KEY PATHOGENIC EVENT OF LUNG INJURY IN BLEOMYCIN-INDUCED PULMONARY FIBROSIS IN A MOUSE MODEL | ||||
| Al-Azhar Journal of Pharmaceutical Sciences | ||||
| Public Titles, Volume 61, Issue 1, March 2020, Page 92-103 PDF (758.16 K) | ||||
| DOI: 10.21608/ajps.2020.86019 | ||||
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| Author | ||||
| Mostafa Sabry* | ||||
| Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt. | ||||
| Abstract | ||||
| Interstitial lung disease (ILD) comprises many chronic lung diseases with various degrees of inflammation and fibrosis. Idiopathic pulmonary fibrosis (IPF) is a specific lung disorder characterized by progressive fibrosis leading to end-stage lung disease, respiratory failure, and fatal outcome. The toll like receptor (TLR) family serves as an important regulatory role in the innate immune system. Recently, several studies implicated TLR signaling in the proinflammatory response of a variety of endogenous and exogenous stimuli within the lung. Innate immune activation via TLR4 contributes to lung injuries but its role in tissue remodeling during ILD is still unclear. The current study aimed to investigate role of lungTLR4, nuclear factor kappa B (NF-kB), transforming growth factor-β (TGF-β) and interleukin 1B (IL1B) in the pathogenesis of IPF. We examined the expression pattern of TLR4, NF-kB, TGF and IL1B after one and three weeks of bleomycin-induced pulmonary fibrosis in a mouse model. Expression of TLR4 and its downstream modulator NF-kB were markedly elevated. Consequently, expression of profibrogenic cytokine TGF-β and inflammatory cytokines IL1B were induced in all grades of pulmonary fibrosis of mice model. Furthermore, there was an increase in interstitial collagen deposition side by side with induction of the activity of some pathophysiological enzymes and uric acid. In conclusion, our findings exhibit the importance of TLR4/NF-kB as significant mediators in fibrotic lung injury and open the door for future studies that can improve the lifestyle of IPF patients. | ||||
| Keywords | ||||
| TLR4; TGF-β; lung; bleomycin; fibrosis; IL1B; ILD; IPF; NF-kB | ||||
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