Cecropin A: investigation of a host defense peptide with multifaceted immunomodulatory activity in a chicken hepatic cell culture

Rege Anna Márton; Csilla Sebők; Máté Mackei; Patrik Tráj; Júlia Vörösházi; Ágnes Kemény; Zsuzsanna Neogrády; Gábor Mátis

doi:10.3389/fvets.2024.1337677

Cecropin A: investigation of a host defense peptide with multifaceted immunomodulatory activity in a chicken hepatic cell culture

Front Vet Sci. 2024 Mar 1:11:1337677. doi: 10.3389/fvets.2024.1337677. eCollection 2024.

Authors

Rege Anna Márton^{1

2}, Csilla Sebők¹, Máté Mackei^{1

2}, Patrik Tráj¹, Júlia Vörösházi¹, Ágnes Kemény^{3

4}, Zsuzsanna Neogrády¹, Gábor Mátis^{1

2}

Affiliations

¹ Division of Biochemistry, Department of Physiology and Biochemistry, University of Veterinary Medicine, Budapest, Hungary.
² National Laboratory of Infectious Animal Diseases, Antimicrobial Resistance, Veterinary Public Health and Food Chain Safety, University of Veterinary Medicine, Budapest, Hungary.
³ Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Pécs, Hungary.
⁴ Department of Medical Biology, Medical School, University of Pécs, Pécs, Hungary.

Abstract

Introduction: Host defense peptides (HDPs) are increasingly referred to as promising candidates for the reduction of the use of conventional antibiotics, thereby combating antibiotic resistance. As HDPs have been described to exert various immunomodulatory effects, cecropin A (CecA) appears to be a potent agent to influence the host inflammatory response.

Methods: In the present study, a chicken primary hepatocyte-non-parenchymal cell co-culture was used to investigate the putative immunomodulatory effects of CecA alone and in inflammatory conditions evoked by polyinosinic-polycytidylic acid (Poly I:C). To examine the viability of the cells, the extracellular lactate dehydrogenase (LDH) activity was determined by colorimetric assay. Inflammatory markers interleukin (IL)-8 and transforming growth factor-ß1 (TGF-ß1) were investigated using the ELISA method, whereas concentrations of IL-6, IL-10, and interferon-γ (IFN-γ) were assayed by Luminex xMAP technology. Extracellular H₂O₂ and malondialdehyde levels were measured by fluorometric and colorimetric methods, respectively.

Results: Results of the lower concentrations suggested the safe application of CecA; however, it might contribute to hepatic cell membrane damage at its higher concentrations. We also found that the peptide alleviated the inflammatory response, reflected by the decreased production of the pro-inflammatory IL-6, IL-8, and IFN-γ. In addition, CecA diminished the levels of anti-inflammatory IL-10 and TGF-ß1. The oxidative markers measured remained unchanged in most cases of CecA exposure.

Discussion: CecA displayed a multifaceted immunomodulatory but not purely anti-inflammatory activity on the hepatic cells, and might be suggested to maintain the hepatic inflammatory homeostasis in Poly I:C-triggered immune response. To conclude, our study suggests that CecA might be a promising molecule for the development of new immunomodulatory antibiotic-substitutive agents in poultry medicine; however, there is still a lot to clarify regarding its cellular effects.

Keywords: antimicrobial peptide; cecropin A; hepatic cell culture; host defense peptide; immunomodulatory; poultry.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The work was financially supported by the Hungarian National Research, Development and Innovation Office (grant number: OTKA FK 134940). In addition, project no. RRF-2.3.1-21-2022-00001 has been implemented with the support provided by the Recovery and Resilience Facility (RRF), financed under the National Recovery Fund budget estimate, RRF-2.3.1-21 funding scheme.