Fasciola hepatica fatty acid binding protein inhibits TLR4 activation and suppresses the inflammatory cytokines induced by lipopolysaccharide in vitro and in vivo.

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TitleFasciola hepatica fatty acid binding protein inhibits TLR4 activation and suppresses the inflammatory cytokines induced by lipopolysaccharide in vitro and in vivo.
Publication TypeJournal Article
Year of Publication2015
AuthorsMartin, I, Cabán-Hernández, K, Figueroa-Santiago, O, Espino, AM
JournalJ Immunol
Volume194
Issue8
Pagination3924-36
Date Published2015 Apr 15
ISSN1550-6606
KeywordsAnimals, Antigens, CD14, Bone Marrow Cells, Cytokines, Extracellular Signal-Regulated MAP Kinases, Fasciola hepatica, Fatty Acid-Binding Proteins, Female, Helminth Proteins, Inflammation, Lipopolysaccharides, Macrophages, Mice, Mice, Knockout, Nitric Oxide Synthase Type II, Phosphorylation, Shock, Septic, Toll-Like Receptor 4
Abstract

TLR4, the innate immunity receptor for bacterial endotoxins, plays a pivotal role in the induction of inflammatory responses. There is a need to develop molecules that block either activation through TLR4 or the downstream signaling pathways to inhibit the storm of inflammation typically elicited by bacterial LPS, which is a major cause of the high mortality associated with bacterial sepsis. We report in this article that a single i.p. injection of 15 μg fatty acid binding protein from Fasciola hepatica (Fh12) 1 h before exposure to LPS suppressed significantly the expression of serum inflammatory cytokines in a model of septic shock using C57BL/6 mice. Because macrophages are a good source of IL-12p70 and TNF-α, and are critical in driving adaptive immunity, we investigated the effect of Fh12 on the function of mouse bone marrow-derived macrophages (bmMΦs). Although Fh12 alone did not induce cytokine expression, it significantly suppressed the expression of IL-12, TNF-α, IL-6, and IL-1β cytokines, as well as inducible NO synthase-2 in bmMΦs, and also impaired the phagocytic capacity of bmMΦs. Fh12 had a limited effect on the expression of inflammatory cytokines induced in response to other TLR ligands. One mechanism used by Fh12 to exert its anti-inflammatory effect is binding to the CD14 coreceptor. Moreover, it suppresses phosphorylation of ERK, p38, and JNK. The potent anti-inflammatory properties of Fh12 demonstrated in this study open doors to further studies directed at exploring the potential of this molecule as a new class of drug against septic shock or other inflammatory diseases.

DOI10.4049/jimmunol.1401182
Alternate JournalJ. Immunol.
PubMed ID25780044
PubMed Central IDPMC4390499
Grant List1SC1AI096108-01A2 / AI / NIAID NIH HHS / United States
R25 GM061838 / GM / NIGMS NIH HHS / United States
R25GM061838 / GM / NIGMS NIH HHS / United States
SC1 AI096108 / AI / NIAID NIH HHS / United States