Amelioration of intestinal colitis by macrophage migration inhibitory factor isolated from intestinal parasites through Toll‐like receptor 2

Abstract

In a previous study, we cloned type II MIFs (As-MIF) from Anisakis simplex 3rd stage larva and expressed a recombinant protein that suppressed allergic airway inflammation via regulatory T (CD4(+) CD25(+) Foxp3(+) T; T(reg) )-cell recruitment. In this study, in an effort to evaluate the function of rAs-MIF on another immune disease, we induced intestinal inflammation in mice using dextran sodium sulphate (DSS) with or without the application of rAs-MIF treatment to the mice. As a consequence, weight losses were recovered, and the value of disease activity index (DAI) was reduced by rAs-MIF treatment during the experimental period. The levels of TGF-β and IL-10 in the spleens and mesenteric lymph nodes (MLN) from the rAs-MIF-treated mice were higher, but the levels of IFN-γ, IL-6 and IL-13 were lower than those of the mice treated with DSS but not with rAs-MIF. Additionally, the T(reg) cells observed were greatly increased in the MLNs of the rAs-MIF-treated mice than those of mice not treated with rAs-MIF. The results of our in vitro experiments showed that the elevated IL-10 production induced by rAs-MIF was generated via toll-like receptor 2. In conclusion, rAs-MIF appears to ameliorate DSS-induced colitis and may prove useful as a therapeutic agent for the treatment of intestinal inflammatory disease.

Helminth Immunomodulation in Autoimmune Disease

“…Paradoxically, mammalian MIF is thought to be pro-inflammatory and involved in a number of inflammatory diseases including asthma, RA, IBD, and psoriasis (65). Two secretory MIF homologs have been identified in nematodes: MIF-1 and MIF-2, possessing 40% and 27% identity with the mammalian protein, respectively (137).…”

Identification and biochemical characterization of macrophage migration inhibitory factor-2 (MIF-2) homologue of human lymphatic filarial parasite, Wuchereria bancrofti

“…Hence, MIF and its homologs of parasites have generated a lot of interest, especially because of their role in the pathogenesis of major diseases such as malaria, leishmaniasis and other parasitic infections (Malu et al, 2011;Rosado and Rodriguez, 2011;Rodríguez et al, 2006;McDevitt et al, 2006;Kamir et al, 2008). Parasite MIF is also considered as a potential therapeutic molecule in the treatment of inflammatory diseases (Cho et al, 2011;Nishihira, 2012;Sanchez et al, 2010), as also a drug target in parasitic diseases.…”

“…These molecules have been reported to play important role in immune evasion by parasites, a strategy for their long term persistence inside the host. Recently, MIF-2 of Anisakis simplex has been reported in the suppression of intestinal colitis and in the up regulation of IL-10 production in the intestinal epithelial cell line, through the activation of Toll like receptor-2 (Cho et al, 2011). Human MIF and parasitic MIF homolog share the same receptor, CD74, for binding to the cell, which gives reminiscence of competition with human MIF.…”

“…(b) Tautomerase activity read at wavelength 475 nm: control reactions dopachrome methyl ester + sodium periodate + elution buffer) and enzyme reaction (dopachrome methyl ester + sodium periodate + recombinant Wba-MIF-2 protein). vitro cellular studies (Cho et al, 2011). Among parasitic diseases, lymphatic filariasis caused by W. bancrofti, B. malayi and Brugia timori is reported as a disease with most complex immunological reactions.…”

Helminthotherapy

“…Hayvan modellerinde kolite karşı etkin olduğu gösterilen helmint salgılarına örnek olarak migrasyon inhibitör faktörü (MIF)-2, sistatinler ve P28GST verilebilir [1] . Bunlardan P28GST'nin T H 2 immün yanıtı indükleyerek kolitte gerilemeye sebep olduğu, aynı etkinin MIF-2 ve sistatin tarafından immün yanıtı düzenleyici yolağı etkileyerek sağlandığı düşünülmektedir [22,37,38] .…”