Pro-inflammatory effects of endogenous and recombinant MDA-7/IL-24 with RGD peptide on human hepatic stellate cells

This is the authors' abstract. We don't add key points for this paper.

Hepatic stellate cells (HSCs) serve as pivotal mediators of liver fibrogenesis. This study investigates the pro-inflammatory effects of melanoma differentiation-associated gene-7/interleukin-24 (MDA-7/IL-24) within both murine and cellular models. By employing the hydrodynamic injection of a plasmid expressing IL-24/mda7 (PMDA-7) in mice, significant inflammatory histopathological alterations were observed in the liver tissue. In human LX-2 HSCs, treatment with recombinant IL-24 (rIL-24), as well as transfection with PMDA-7 or RGD-modified PMDA-7-RGD plasmids, resulted in an increased expression of pro-inflammatory cytokines (IL-1β, IL-6, IL-17, IL-18, IL-23) and regulatory molecules (SOCS1, SOCS3). Importantly, the RGD-modified variant exhibited the most pronounced effects, with PMDA-7-RGD inducing the highest levels of IL-1β, IL-6, IL-17, and IL-18 expression, whereas rIL-24 was noted to most effectively upregulate IL-23 (P < 0.05). These findings substantiate that MDA-7/IL-24 exerts pro-inflammatory effects on HSCs, which are further amplified by RGD conjugation, thus suggesting its potential involvement in the pathogenesis of liver inflammation and fibrosis.