Inhaled [D-Ala²]-Dynorphin 1-6 Prevents Hyperacetylation and Release of High Mobility Group Box 1 in a Mouse Model of Acute Lung Injury

Figure 6

Schematic diagram illustrating the modes of leytragin action in a mouse model of LPS-induced pulmonary inflammation. (a) LPS via TLR4 triggers HMGB1 hyperacetylation, followed by HMGB1’s translocation from the nucleus to the cytoplasm and then to the extracellular milieu [13, 24]. (b) Leytragin via DOR upregulates SIRT1 expression, causing deacetylation of HMGB1 [16–18], thereby redirecting HMGB1 to the nucleus and preventing its release into the extracellular milieu. (c) Leytragin inhibits the LPS-induced production of proinflammatory cytokines, as well as HMGB1 release, thereby inhibiting the progression to cytokine storms and lethal ARDS.

(a)

(b)

(c)