Regulation of Toll-like receptor 4 expression in mouse colon by macrophage migration inhibitory factor

Abstract

Recent studies have indicated that macrophage migration inhibitory factor (MIF) and Toll-like receptor (TLR) play an important role in the regulation of innate immune responses. In this study, we investigated the effect of MIF on the expression of TLR4, a receptor that recognizes lipopolysaccharide, in colon using MIF-deficient mice. TLR4 mRNA expression in the colon tissues was determined by northern blot analysis. Western blot analysis and immunohistochemistry in the colon tissues were performed to evaluate the expression of TLR4 protein. The expressions of TLR4 mRNA and protein were remarkably down-regulated in colon tissues of MIF-deficient mice compared with wild-type mice and up-regulated by treatment with recombinant MIF. Immunohistochemical study revealed the presence of TLR4-positive staining in mononuclear cells in the lamina propria and intraepithelial mononuclear cells as well as weak staining in epithelial cells and crypts in colon tissues of wild-type mice. In contrast, MIF-deficient mice did not show TLR4-positive staining in the colonic mucosa. In MIF-deficient mice injected with recombinant mouse MIF (rMIF), TLR4-positive staining cells were observed in colon tissues similar to the findings in wild-type mice. Administration of dextran sulfate sodium (DSS) up-regulated the expression of TLR4 in the colons of WT mice but not in those of MIF-deficient mice. Furthermore, pretreatment with rMIF up-regulated the expression of TLR4 in response to DSS in MIF-deficient mice. Our results suggest that MIF affects the expression of TLR4 in mouse colon under both normal and colitic conditions.

Inhibition of proprotein convertase subtilisin/kexin type 9 attenuates 2,4,6‐trinitrobenzenesulfonic acid‐induced colitis via repressing toll‐like receptor 4/nuclear factor‐kappa B

“…33 TLR4 was upregulated in patients with IBD 34 and colitis model. 35 NF-κB was also upregulated in TNBSinduced colitis. 2 In line with previous study, 36 the present study showed that TNBS stimulated TLR4/NF-κB activation, thus leading to release of proinflammatory factors and promotion of inflammatory response.…”

Qing Hua Chang Yin exerts therapeutic effects against ulcerative colitis through the inhibition of the TLR4/NF-κB pathway

“…TLR4 is activated by recognizing PAMPs in bacteria, which in turn triggers signaling cascades leading to the activation of NF-κB (12). TLR4 is expressed at low levels in normal intestines but is increased in mice with DSS-induced colitis (13,14) and in patients with IBD (15,16), which may contribute to the initiation or perpetuation of intestinal inflammation. Previous studies have demonstrated that TLR4 functions as a mediator of intestinal inflammation (17) and that the blockade of TLR4 ameliorates DSS-induced colitis (18).…”

“…Upon ligand binding, TLR4 undergoes a conformational change and dimerizes, recruiting adaptor proteins, such as myeloid differentiation primary response gene 88 (MyD88), which in turn activates NF-κB, transducing the immune-related signals to the nucleus (10,11). Due to its essential role in the pathogenesis of inflammatory diseases, including IBD (12)(13)(14)(15)(16)(17)(18), modulation of the TLR4/NF-κB signaling pathway may be a main target for the treatment of inflammation.…”

Assessment of Toll-like Receptors in the Ileum of Weanling Pigs- Responses to Feed Antibiotic Chlortetracycline and Gnotobiotic Conditions

“…In this study, both human TLR-2 and -9 antibodies very effectively detected the presence of porcine TLR-2 and -9 in the ileal tissues from all the three groups of animals; however, we were unable to detect porcine TLR-4 and -5 with polyclonal human TLR-4 and -5 antibodies. One possible explanation might be a longer fixation of ileal tissues for 48 hours in formalin in the present study compared to 16 hours used in earlier studies [42,69]. This might have resulted in non-retrieval of TLR-4 and -5 antigens with the treatment procedure used in this study.…”