| First Author | Dong W | Year | 2018 |
| Journal | Biochem J | Volume | 475 |
| Issue | 22 | Pages | 3687-3706 |
| PubMed ID | 30373763 | Mgi Jnum | J:268908 |
| Mgi Id | MGI:6270098 | Doi | 10.1042/BCJ20180483 |
| Citation | Dong W, et al. (2018) Potential role of a series of lysine-/leucine-rich antimicrobial peptide in inhibiting lipopolysaccharide-induced inflammation. Biochem J 475(22):3687-3706 |
| abstractText | Antimicrobial peptides have broad-spectrum killing activities against bacteria, enveloped viruses, fungi and several parasites via cell membrane permeation and exhibit primarily immunomodulatory and anti-infective functions in their interactions with host cells. However, the mechanism underlying their anti-inflammatory activity remains to be elucidated. L-K6, an analog of temporin-1CEb isolated from the skin secretion of Rana chensinensis, has demonstrated a wide range of antimicrobial activities against gram-negative and gram-positive bacteria. In this study, the potent anti-inflammatory mechanism of L-K6 and its analogs in lipopolysaccharide (LPS)-stimulated human macrophage U937 cells were evaluated. We found that L-K6 suppressed the expression of inflammatory factors by two downstream signaling components in the MyD88-dependent pathway, including the mitogen-activated protein kinases (MAPKs) and the NF (nuclear factor)-kappaB signaling pathway, but its analog L-K5, which had the same amino acid sequence as L-K6 but no Lys residue at the -COOH terminal, only inhibited the phosphorylation of I-kappaB and NF-kappaB. Importantly, L-K6 and L-K5 were actively taken up by U937 cells through an independent cell membrane disruption mechanism and were eventually localized to the perinuclear region. The L-K6 uptake process was mediated by endocytosis, but L-K5 was specifically taken up by U937 cells via TLR4 endocytosis. Our results demonstrated that L-K6 can neutralize LPS and diassociate LPS micelles to inhibit LPS from triggering the proinflammatory signaling pathway, and by partially inhibiting inflammatory responses by the intracellular target. However, L-K5 may mainly inhibit proinflammatory responses by intracellular reporters to modulate the NF-kappaB signaling pathway. |
