The protective and immunomodulatory effects of hypothalamic proline-rich polypeptide galarmin against methicillin-resistant Staphylococcus aureus infection in mice

Abstract

The present research summarizes the protective and immunomodulatory activity of hypothalamic proline-rich polypeptide galarmin against methicillin-resistant Staphylococcus aureus (MRSA). The protective effect of galarmin was shown on MRSA-infected animals' survival and weight loss recovery. The immunological impact of galarmin was evaluated in terms of immunocompetent cell recruitment, serum immunoglobulins, complement components C3 and C4, and pro- and anti-inflammatory cytokines (IL-6, IL-8, IL-10, IL-1b, TNFa, and KC) secretion. Galarmin efficiently protects mice against lethal MRSA infection (100% of survival vs. 0% in the untreated group) when intramuscularly injected 24 h before infection and during the 1-h post-infection period at a concentration of 1 μg per mouse, while its higher concentrations (5 and 10 μg) were protective when injected in parallel to the infection process. The protective effect of galarmin was not due to a direct effect on MRSA, but should be attributed to an action on the host response to infection. Galarmin significantly increased and modulated the levels of IL-6, IL-8, IL-1b, IL-10, and KC in both peritoneal lavages and blood, leukocyte and platelet counts, lymphocytes percentage, serum IgM and IgG, and complement C3 and C4 components secretion. The experimental results allow concluding that galarmin is a powerful immunomodulatory and protective agent for the in vivo prophylaxis and treatment of MRSA-induced infection.

The Antioxidant Polysaccharide from Semiaquilegia adoxoides (DC.) Makino Adjusts the Immune Response of Mice Infected by Bacteria

“…IgM mainly exists in the blood of organisms and is also the earliest antibody in the initial humoral immune response, which plays a vital role in the immune response. Studies have shown that the levels of IL-1, IL-6, TNF-α, and IgM in mice increased significantly in the acute stage of E. coli and S. aureus infection [30][31][32][33]. Our test results are consistent with those reported above.…”

Caprine Bactenecins as Promising Tools for Developing New Antimicrobial and Antitumor Drugs

“…On the face of it, this looks contradictory to the observation that PR-AMPs are predominantly active against Gram-negative bacteria in vitro. However, the protective effect of the peptide was in fact not due to a direct killing of bacteria, but via its immunomodulatory action: immunocompetent cell recruitment and modulation of the release of pro-and anti-inflammatory cytokines (IL-6, IL-8, IL-10, IL-1b, TNFa) (Durgaryan et al, 2012).…”

Morpho‑functional study of the hypothalamic proline‑rich polypeptide apoptotic activity against mouse Ehrlich ascites carcinoma

“…1B and C). On day 11 post-inoculation, the total number of cells increased from 5x10 6 to 6.5x10 6 , of which 93% were viable in the 24 h control, while in the PRP-1-treated samples, that number was 5x10 6 , with only 49% of viable cells, thus indicating an inhibition of viable cells by 44% caused by PRP-1 (Fig. 2B and C).…”

“…Concurrently, the number of viable EAC cells treated with PRP-1 was decreased compared with that in the control group. On day 7 post-inoculation, the number of total cells was 5x10 6 , and increased to 8x10 6 , with viable cells comprising 88% of the cell population, whereas in the 0.1 µg/ml PRP-1-treated samples, the total number of cells was reduced to 4x10 6 , where viable cells accounted for 66% of the total population. Thus, PRP-1 inhibited the growth of viable cells by 22% (Fig.…”

“…PRPs are synthesized from a common precursor, namely neurophysin vasopressin-associated glycoprotein. The mTORC1 inhibitor proline-rich polypetide 1 (PRP-1; also known as galarmin) is a short 15-amino acid neuropeptide (sequence, Ala-Gly-Ala-Pro-Glu-Pro-Ala-Glu-Pro-Ala-Gl n-Pro-Gly-Val-Tyr) with neuroprotective, immunomodulatory (3,4), antiviral, anti-inflammatory (5), antibacterial (6), hematopoietic (7) and antitumor properties (8)(9)(10)(11)(12)(13)(14).…”