Lipopolysaccharide Upregulated Intestinal Epithelial Cell Expression of Fn14 and Activation of Fn14 Signaling Amplify Intestinal TLR4-Mediated Inflammation

Abstract

TLR4 in intestinal epithelial cells has been shown both inflammatory and homeostatic roles following binding of its cognate ligand lipopolysaccharide (LPS). TWEAK-Fn14 axis plays an important role in pathologies caused by excessive or abnormal inflammatory responses. This study aimed to evaluate potential cross-talk between TLR4 and TWEAK/Fn14 system in porcine small intestinal epithelial cells. Our in vivo results showed that, compared with the age-matched normal control piglets, increased expression of Fn14 in epithelium and decreased TWEAK expression in lamina propria were detected in the small intestinal of piglets stimulated with LPS. Consistent with this finding, treatment with LPS increased the expression of Fn14 and TLR4 while decreased TWEAK expression in porcine small intestinal epithelial cell lines SIEC02. Interestingly, modulating Fn14 activation using agonistic anti-Fn14 decreased TLR4-mediated TNF-α production by SIEC02. In addition, pretreatment of LPS-stimulated SIEC02 with recombinant TWEAK protein suppresses the expression of Fn14 and TNF-α and inhibits the negative impact of LPS on the tight junctional protein occludin expression. In conclusion, this study demonstrates that the TWEAK-independent Fn14 activation augments TLR4-mediated inflammatory responses in the intestine of piglets. Furthermore, the TWEAK-dependent suppression of Fn14 signaling may play a role in intestinal homeostasis.

MicroRNA expression profiling of goat peripheral blood mononuclear cells in response to peste des petits ruminants virus infection

“…Protein homogenates from goat PBMC were extracted as previously described [ 24 ]. Briefly, the cells were lysed for 20 min on ice in ice-cold lysis buffer (4906837001, Roche).…”

Changes in bacterial community and expression of genes involved in intestinal innate immunity in the jejunum of newborn lambs during the first 24 hours of life

“…It is well known that TLR4 recognizes LPS, a major component of the gram-negative bacterial cell wall. Increased TLR4 expression was induced by LPS in the porcine intestinal epithelial cell (Qi et al, 2017). A previous study indicated that mRNA abundance of jejunal TLR4 was decreased and intestinal injury was alleviated in weanling pigs supplemented with glutamate (Qin et al, 2018).…”

TWEAK/Fn14 Is Overexpressed in Crohn’s Disease and Mediates Experimental Ileitis by Regulating Critical Innate and Adaptive Immune Pathways

“…Because Fn14 is expressed in both nonhematopoietic (intestinal epithelial cells) 27 and hematopoietic (immune cells) 18 populations, we quantified separately the contribution of Fn14 that is derived from either cellular compartment in the development of chronic intestinal inflammation. In particular, we generated 4 groups of bone marrow (BM) chimeras that expressed either: (1) no components of the Fn14 receptor (knockout [KO] > KO mice); (2) only hematopoietic-derived Fn14 receptors (WT > KO mice); (3) only non–hematopoietic-derived Fn14 receptor (KO > WT mice); or (4) both hematopoietic and non–hematopoietic-derived Fn14 receptors (WT > WT mice) (Figure 4 A ).…”