PMID- 30322527 OWN - NLM STAT- MEDLINE DCOM- 20190130 LR - 20190130 IS - 1873-2542 (Electronic) IS - 0378-1135 (Linking) VI - 225 DP - 2018 Nov TI - The immunomodulatory effect of antimicrobial peptide HPA3P restricts Brucella abortus 544 infection in BALB/c mice. PG - 17-24 LID - S0378-1135(18)30979-9 [pii] LID - 10.1016/j.vetmic.2018.09.005 [doi] AB - The discovery of antimicrobial peptides (AMPs) in recent years has been promising for the treatment of multidrug resistant pathogenic microbes. Brucellosis is still considered one of the most common zoonoses in the world. In this study, we evaluated the effect HPA3P peptide in the bacterial uptake and intracellular growth of Brucella abortus (B. abortus) 544 in murine macrophages RAW 264.7. HPA3P was further utilized in a mouse model for infection and treatment. This peptide did not show cytotoxicity or bactericidal effect to B. abortus. However, it inhibited bacterial internalization at 0, 15 and 30 min incubation at two different doses at 12 and 24 muM as well as reduced intracellular growth after 2, 24 and 48 h incubation. Mice treated with HPA3P demonstrated a significant 1.01-log reduction (P < 0.0001) and spleen weight reduction compared to the nanocarrier control (P < 0.01). Significant increases in key cytokines Interferon-gamma (IFN-gamma) and Tumor necrosis factor (TNF) at 3, 7 and 14 days post-infection were observed in HPA3P treated mice similar to the antibiotic control group with both compared to the nanocarrier control. Monocyte chemoattractant protein-1 (MCP-1) was also heightened at 14 days post-infection. Histopathological analysis also suggests reduced bacterial granuloma in the liver and spleens of HPA3P treated group compared with the nanocarrier control group. In this study, the modulation of crucial cytokines IFN-gamma and TNF might have led to a considerable reduction in the proliferation of B. abortus in a mouse model of brucellosis. Further investigation might be required to maximize the efficacy of HPA3P treatment in murine brucellosis. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Arayan, Lauren Togonon AU - Arayan LT AD - Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, 52828, Republic of Korea. FAU - Kim, Hyeun Bum AU - Kim HB AD - Department of Animal Resources Science, Dankook University, Cheonan, 31116, Republic of Korea. FAU - Bernardo Reyes, Alisha Wehdnesday AU - Bernardo Reyes AW AD - Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, 52828, Republic of Korea. FAU - Xuan Huy, Ngoc Tran AU - Xuan Huy NT AD - Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, 52828, Republic of Korea. FAU - Hong, Il Hwa AU - Hong IH AD - Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, 52828, Republic of Korea. FAU - Lee, Kangseok AU - Lee K AD - Department of Life Science, Chung-Ang University, Seoul, 06974, Republic of Korea. FAU - Yeom, Ji-Hyun AU - Yeom JH AD - Department of Life Science, Chung-Ang University, Seoul, 06974, Republic of Korea. FAU - Park, Yoonkyung AU - Park Y AD - Department of Biomedical Science, Chosun University, Gwangju, 61452, Republic of Korea. FAU - Kim, Suk AU - Kim S AD - Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, 52828, Republic of Korea. Electronic address: kimsuk@gnu.ac.kr. LA - eng PT - Journal Article DEP - 20180913 PL - Netherlands TA - Vet Microbiol JT - Veterinary microbiology JID - 7705469 RN - 0 (Anti-Bacterial Agents) RN - 0 (Cytokines) RN - 0 (Immunologic Factors) RN - 0 (Peptides) RN - 0 (Tumor Necrosis Factor-alpha) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Animals MH - Anti-Bacterial Agents/*pharmacology MH - Brucella abortus/*drug effects/growth & development/immunology MH - Brucellosis/*immunology/microbiology MH - Cytokines/immunology MH - Disease Models, Animal MH - Immunologic Factors/administration & dosage/pharmacokinetics MH - Interferon-gamma/immunology MH - Liver/microbiology/pathology MH - Macrophages/*drug effects/immunology/microbiology MH - Mice MH - Mice, Inbred BALB C MH - Peptides/*administration & dosage/chemical synthesis/immunology/*pharmacology MH - Spleen/microbiology/pathology MH - Tumor Necrosis Factor-alpha/immunology OTO - NOTNLM OT - Antimicrobial peptide OT - Brucella abortus OT - Cytokines OT - HPA3P EDAT- 2018/10/17 06:00 MHDA- 2019/01/31 06:00 CRDT- 2018/10/17 06:00 PHST- 2018/08/22 00:00 [received] PHST- 2018/09/11 00:00 [revised] PHST- 2018/09/12 00:00 [accepted] PHST- 2018/10/17 06:00 [entrez] PHST- 2018/10/17 06:00 [pubmed] PHST- 2019/01/31 06:00 [medline] AID - S0378-1135(18)30979-9 [pii] AID - 10.1016/j.vetmic.2018.09.005 [doi] PST - ppublish SO - Vet Microbiol. 2018 Nov;225:17-24. doi: 10.1016/j.vetmic.2018.09.005. Epub 2018 Sep 13.