Roles of NET Peptides With Known Antimicrobial Activity and Toxicity in Immune Response

Antimicrobial peptides (AMPs) are crucial components of the innate immune system in all living organisms, playing a vital role in the body's defense against diseases and infections. The immune system's primary functions include preventing disease-causing agents from entering the body and eliminating them without causing harm. These peptides exhibit broad-spectrum activity against bacteria, viruses, fungi, parasites, and cancer cells. They are secreted by innate and epithelial cells and contribute to host defense by inducing cellular activities such as cell migration, proliferation, differentiation, cytokine production, angiogenesis, and wound healing. In response to the growing challenge of bacterial resistance to antimicrobial agents, alternative drugs and new antibacterial molecules are being explored. In a previous study, NET AMPs were synthesized and their antimicrobial effects were determined. The current study extends this work by assessing the effects of these peptides on the immune system through cell culture experiments and ELISA. Specifically, the study investigated how different concentrations of these peptides influence the secretion of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) in mouse macrophages. Among the synthesized peptides, NET1 and NET2 demonstrated low cytotoxicity in TIB-71 RAW 264.7 macrophages. These peptides induced an anti-inflammatory response and reduced IL-6 expression in the absence of LPS stimulation, while simultaneously increasing IFN-γ and TNF-α secretion. These findings suggest that NET1 and NET2 peptides possess both anti-inflammatory and pro-inflammatory properties, highlighting their potential role in modulating immune responses.