Interleukin-1 Receptor / Toll-like Receptor Signaling: A Therapeutic Target for Pulmonary Inflammatory Disease
Year: 2008
Type: dissertation
Abstract: Numerous studies have shown the importance of interleukin- 1[Beta] (IL-1[Beta] and IL-1 receptor (IL-1R) / Toll-like receptor (TLR) signaling in the development of pulmonary inflammation, including acute lung injury (ALI) and asthma. Thus, inhibition of IL-1[Beta] receptor signaling is a potential therapeutic target in the treatment of ALI and asthma. EM-163 is a small organic molecular mimic synthesized by the Rebek laboratory of the Scripps Research Institute based on molecular modeling of the crystal structure of the IL-1[Beta] receptor with its adaptor protein. The Rebek laboratory has shown that this compound inhibits IL-1[Beta] signaling, in vitro. In vivo studies were done in C57BL/6 or BALB/c mice using a LPS model of ALI and an ovalbumin model of asthma. Inhibition of IL-1 signaling in these models was done to determine the efficacy of EM-163 in the development of ALI and modulating allergic inflammation in an asthma model. In vitro studies are being conducted to determine specificity of EM-163 for targeting IL-1R signaling. In the ALI model, EM-163 showed attenuation of LPS-induced neutrophilic inflammation, capillary leak, and loss of lung compliance. In the ovalbumin model of asthma, IL-1[Beta] inhibition attenuated airway hyperresponsiveness in C57BL/6 mice, while effects on inflammation were minimal. In BALB/c mice, airway inflammation was reduced. These results suggest EM- 163 will be effective in treatment of ALI and asthma, supporting the targeting of IL-1R signaling in the treatment of inflammatory disease
Author: Karen Laguren Saroca
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2135479528