Fasciola hepatica fatty acid binding protein inhibits TLR4 activation and suppresses the inflammatory cytokines induced by lipopolysaccharide in vitro and in vivo.
Submitted by Kimberly Cabán-Hernández on
Title | Fasciola hepatica fatty acid binding protein inhibits TLR4 activation and suppresses the inflammatory cytokines induced by lipopolysaccharide in vitro and in vivo. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Martin, I, Cabán-Hernández, K, Figueroa-Santiago, O, Espino, AM |
Journal | J Immunol |
Volume | 194 |
Issue | 8 |
Pagination | 3924-36 |
Date Published | 2015 Apr 15 |
ISSN | 1550-6606 |
Keywords | Animals, 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. |
DOI | 10.4049/jimmunol.1401182 |
Alternate Journal | J. Immunol. |
PubMed ID | 25780044 |
PubMed Central ID | PMC4390499 |
Grant List | 1SC1AI096108-01A2 / 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 |