Increased Cerebral Tff1 Expression in Two Murine Models of Neuroinflammation

Abstract

Background/Aims: The trefoil factor family (TFF) peptide TFF1 is a typical secretory product of the gastric mucosa and a very low level of expression occurs in nearly all regions of the murine brain. TFF1 possesses a lectin activity and binding to a plethora of transmembrane glycoproteins could explain the diverse biological effects of TFF1 (e.g., anti-apoptotic effect). It was the aim to test whether TFF expression is changed during neuroinflammation. Methods: Expression profiling was performed using semi-quantitative RT-PCR analyses in two murine models of neuroinflammation, i.e. Toxoplasma gondii-induced encephalitis and experimental autoimmune encephalomyelitis (EAE), the latter being the most common animal model of multiple sclerosis. Tff1 expression was also localized using RNA in situ hybridization histochemistry. Results: We report for the first time on a significant transcriptional induction in cerebral Tff1 expression in both T. gondii-induced encephalitis and EAE. In contrast, Tff2 and Tff3 expression were not altered. Tff1 transcripts were predominantly localized in the internal granular layer of the cerebellum indicating neuronal expression. Furthermore, also glial cells are expected to express Tff1. Characterization of both experimental models by expression profiling (e.g., inflammasome sensors, inflammatory cytokines, microglial marker Iba1, ependymin related protein 1) revealed differences concerning the expression of the inflammasome sensor Nlrp1 and interleukin 17a. Conclusion: The up-regulated expression of Tff1 is probably the result of a complex inflammatory process as its expression is induced by tumor necrosis factor α as well as interleukins 1β and 17. However on the transcript level, Tff1^KO mice did not show any significant signs of an altered immune response after infection with T. gondii in comparison with the wild type animals.

Transcriptional Responses in the Murine Spleen after Toxoplasma gondii Infection: Inflammasome and Mucus-Associated Genes

“…infection (129/Sv background). This is in line with previous reports that Nlrp1a and Nlrp1c expression is lacking in certain 129S1 mouse strains [17,32]. …”

“…T. gondii infection (encephalitis model), respectively [14,17]. In the present study, we continued our previous work and investigated the spleen of Tff3 KO mice after oral T. gondii infection because Tff3 is known to be expressed also in the spleen [14,21,22].…”

“…This is in contrast to the expression pattern in the brain four weeks after i.p. T. gondii infection, where at least Nlrp3, Nlrc4, Nlrc5, and Mnda were strongly upregulated ( p ≤ 0.001) [17]. …”

“…T. gondii infection caused a significant induction of pattern-recognition receptors (PRRs) in the brain, particularly members of the NOD-like receptors and of the HIN200 family [17]. These intracellular sensors are, together with procaspase-1 and the adaptor protein ASC, typical constituents of inflammasomes [18,19,20].…”

“…The corresponding gene products belong to an interactome protecting mucous epithelia. Particularly interesting is the expression of TFF1 because it has been shown to be typically upregulated during various chronic inflammatory processes [14,17]. …”