title: Cell-penetrating peptides can confer biological function: regulation of inflammatory cytokines in human monocytes by MK2 inhibitor peptides.
abstract: Cell-penetrating peptides have been used as a method of delivering biologically active peptide for over two decades. In this paper, we covalently attached four different cell-penetrating peptides to a peptide that inhibits a kinase important in inflammation, mitogen-activated protein kinase activated protein kinase 2 (MAPKAP2 or MK2). We evaluated the specificity, toxicity, and functionality of these therapeutics in an in vitro model of inflammation using THP-1 monocytes. When treated with the MK2 peptide inhibitors, activated THP-1 human monocytes challenged with lipopolysaccharide (LPS) showed a decrease in TNF-α and IL-6 excretion without apparent toxicity. In addition, western blot analysis revealed decreases in the phosphorylation of heat shock protein 27 (HSP27), a downstream substrate of MK2. These results suggested that our peptides inhibited MK2 activity in vitro and should be investigated further as a potential therapeutic for applications involving inflammation. Furthermore, our results suggested that cell-penetrating peptides can be bioactive.
authors: Weldon School of Biomedical Engineering, Purdue University, 206 S Martin Jischke Drive, West Lafayette, IN 47907, USA.
authors: Jamie L
authors: JL
authors: Brugnano
authors: Burke K
authors: BK
authors: Chan
authors: Brandon L
authors: BL
authors: Seal
authors: Alyssa
authors: A
authors: Panitch