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Eur J Microbiol Immunol (Bp). 2018 May 23;8(2):34-40. doi: 10.1556/1886.2018.00006. eCollection 2018 Jun 25.

Anti-inflammatory Effects of the Octapeptide NAP in Human Microbiota-Associated Mice Suffering from Subacute Ileitis.

Author information

1
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Microbiology and Infection Immunology, Berlin, Germany.
2
Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Aviv University, Aviv, Israel.
3
Institute of Inflammation and Neurodegeneration, Medical Faculty, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.

Abstract

The octapeptide NAP is well known for its neuroprotective properties. We here investigated whether NAP treatment could alleviate pro-inflammatory immune responses during experimental subacute ileitis. To address this, mice with a human gut microbiota were perorally infected with one cyst of Toxoplasma gondii (day 0) and subjected to intraperitoneal synthetic NAP treatment from day 1 until day 8 postinfection (p.i.). Whereas placebo (PLC) control animals displayed subacute ileitis at day 9 p.i., NAP-treated mice exhibited less pronounced pro-inflammatory immune responses as indicated by lower numbers of intestinal mucosal T and B lymphocytes and lower interferon (IFN)-γ concentrations in mesenteric lymph nodes. The NAP-induced anti-inflammatory effects were not restricted to the intestinal tract but could also be observed in extra-intestinal including systemic compartments, given that pro-inflammatory cytokines were lower in liver, kidney, and lung following NAP as compared to PLC application, whereas at day 9 p.i., colonic and serum interleukin (IL)-10 concentrations were higher in the former as compared to the latter. Remarkably, probiotic commensal bifidobacterial loads were higher in the ileal lumen of NAP as compared to PLC-treated mice with ileitis. Our findings thus further support that NAP might be regarded as future treatment option directed against intestinal inflammation.

KEYWORDS:

Toxoplasma gondii; activity-dependent neuroprotective protein (ADNP); extra-intestinal and systemic immune responses; fecal microbiota transplantation; host immunity; host-pathogen interactions; human gut microbiota; intestinal; octapeptide NAP; secondary abiotic (gnotobiotic) mice; subacute ileitis

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