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SessionsBeetz, Emil - year 5 University of Veterinary Medicine Budapest, Department of Physiology and Biochemistry Supervisor: Gábor Mátis Dr. Antimicrobial resistance has increased interest in alternative or complementary antimicrobial strategies. Antimicrobial peptides, also called host-defence peptides can serve as promising candidates in combating infections in animal farming. Cathelicidins are host-defence peptides with both antimicrobial and immunomodulatory properties, and their biological effects depend strongly on concentration and cellular context. The present study investigated the effects of cathelicidin-2 (CATH-2) in porcine hepatocyte – non parenchymal cell co-cultures under basal and lipopolysaccharide (LPS)-stimulated conditions. Cultures were treated with CATH-2 at 10, 20, or 50 µmol/L, either alone or in combination with LPS. Cellular metabolic activity, extracellular H₂O₂ and malondialdehyde concentrations, and the inflammatory mediators interleukin (IL)-1β, IL-6, IL-12 and tumor necrosis factor (TNF)-α were assessed. CATH-2 elicited concentration-dependent cellular and immunological responses. The highest concentration, 50 µmol/L, significantly reduced cellular metabolic activity, indicating that high peptide concentrations can adversely affect cellular function. The cytokine response was not uniform. Low concentrations generally stimulated selected inflammatory mediators, whereas higher concentrations tended to suppress several cytokine responses. For example, 10 µmol/L CATH-2 increased IL-6 under basal conditions but reduced the LPS-induced IL-6 response. IL-12 also showed a concentration-dependent pattern, with stimulation at low concentration and suppression at 50 µmol/L. In contrast, IL-1β increased at the highest concentration, demonstrating that CATH-2 cannot be classified simply as pro- or anti-inflammatory. Overall, the results demonstrate that CATH-2 exerts complex, concentration-dependent immunomodulatory effects in porcine hepatic cultures. Lower concentrations may support selected immune responses, whereas higher concentrations can suppress inflammatory signalling but may also impair cellular function. These observations contribute to a better understanding of cathelicidin biology and may support further investigation of antimicrobial peptides as complementary approaches to conventional antimicrobial therapy. List of lectures |