Myeloid differentiation protein 2

There are numerous indications that MD2 is associated with numerous acute and chronic inflammatory reactions and can also be seen as a potential and useful therapeutic target for various inflammatory diseases. For example, MD2 plays an important role in inflammation caused by sensitization to cat dander and various pollens.

Versch. Authors report that MD2 is involved in the development of non-alcoholic fatty liver disease and in steatosis and fibrosis caused by methionine and choline deficiency (Zhang Y et al. 2019). Furthermore, MD2 is involved in mediating Ang II-induced cardiac and renal inflammation by directly binding to Ang II and activating the TLR4/myeloid differentiation primary response 88 (MyD88) signaling pathway, which is independent of the AT1 receptor. In addition, L6H21, an inhibitor of MD2, protects against Ang II-induced cardiac and renal damage both in vitro and in vivo (Zhang Y et al. 2019).

1. Dziarski R et al. (2001) MD-2 enables Toll-like receptor 2 (TLR2)-mediated responses to lipopolysaccharide and enhances TLR2-mediated responses to Gram-positive and Gram-negative bacteria and their cell wall components. J Immunol 166:1938-1944.
2. Kim HM et al. (2007) Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran. Cell 130:906-917.
3. Qian J et al. (2021) Myeloid differentiation protein 2 mediates angiotensin II-induced inflammation and mesenchymal transition in vascular endothelium. Biochim Biophys Acta Mol Basis Dis 1867:166043.
4. Shimazu R et al. (1999) MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. J Exp Med 189:1777-1782.
5. Zhang Y et al. (2019) Myeloid Differentiation Protein 2 Mediates Angiotensin II-Induced Liver Inflammation and Fibrosis in Mice. Molecules 25:25.